ISMB/ECCB Stockholm 2009

BioPathways SIG: Nicolas Le Novére "The Systems Biology Graphical Notation"

supposedly biologist-friendly pathway maps are completely unintelligible - Ruchira S. Datta

by contrast, electric circuit diagrams, even very complex ones, can be understood by high school students - Ruchira S. Datta

Systems Biology Graphical Notation http://sbgn.org a limited number of well-defined symbols for biochemical and cellular events - Ruchira S. Datta

3 languages: process diagrams, entity relationships, and activity flow - Ruchira S. Datta

Thanks for updating us - I'm reading with interest from the DAM SIG room in between talks! - Allyson Lister

process diagrams: biochemistry; entity relationships: molecular biology; activity flow: physiology/genetics - Ruchira S. Datta

we're "projecting" the biological process onto different dimensions (the different languages) - Ruchira S. Datta

process diagrams: entity pool nodes (things that can be counted): containers, and process nodes: pipes - Ruchira S. Datta

also connecting arcs, which connect the various nodes w/ logical operators - Ruchira S. Datta

syntactic rules define what can connect with what, and diagram rules show how to render well-formed expressions - Ruchira S. Datta

can contract large diagrams into small ones - Ruchira S. Datta

color is strictly insignificant, so can photocopy diagrams - Ruchira S. Datta

entity relationships can be viewed as rules - Ruchira S. Datta

a process diagram representation of the same process would result in combinatorial explosion; the rule expresses this much more compactly - Ruchira S. Datta

activity flow never represents molecules, only the activities of those molecules - Ruchira S. Datta

have also annotations (not strictly part of SBGN), e.g., GO annotations - Ruchira S. Datta

SBGN is supported by many tools - Ruchira S. Datta

new version is about to be released - Ruchira S. Datta

have upcoming fora and hackathons - Ruchira S. Datta

it is compatible with BioPAX - Ruchira S. Datta

SBGN is more concerned about the graphic representation, so you can import BioPax pathways and visualize them with SBGN - Michael Kuhn

Science Daily summary of the August 8 Nature Biotechnology article: http://www.sciencedaily.com/release... reshared from Jenny Morman http://ff.im/6uWIo - Ruchira S. Datta

Iddo Friedberg to ISMB/ECCB Stockholm 2009, The Life Scientists

Absolut standards: report from the Metagenomics Metadata and Metaanalysis 2009 meeting. Part 1 - http://bytesizebio.net/index...

July 20 - Comment - Like - Share

Pawel Szczesny and Neil Saunders liked this

ISMB/ECCB

TT26: Nicolas Le Noväre - BioModels Database, a database of curated and annotated quantitative models with Web Services and analysis tools

June 29 - Comment - Like - Share

duprat julien, Melanie and Khader Shameer liked this

Lots of things are called models. He's NOT going to talk about HMM, Bayesian models, sailboat models, supermodels :) - Allyson Lister

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Models and their description/metadata need to be accessible - Allyson Lister

Models have to be encoded in SBML and follow the MIRIAM guidelines - Allyson Lister

There's been a steady increase in the numbers of models in BioModels. There are about 35000 reactions and about 400 models. - Allyson Lister

Standard search functionality available from their website at the EBI (http://www.ebi.ac.uk/biomodels) - Allyson Lister

Can export in CellML, BioPAX and others (though the SBML is the curated, perhaps more "trusted", version). - Allyson Lister

You can also just extract portions of the models: these will end up as valid SBML models in their own right. - Allyson Lister

Blog post: http://themindwobbles.wordpress.com/2009... - Allyson Lister

@Alyson: Sorry to be picky, but the abstract says: "Models are accepted in two common formats, SBML and CellML." :-) - Dagmar

@Dagmar - good point. I thought so as well, but that's what Nicolas said. Can we say it's his fault for saying the wrong thing about his database? ;) (If indeed it is the wrong thing?) - Allyson Lister

ISMB/ECCB

HL30: Robert Murphy - Automated Analysis of Patterns in Human Protein Atlas Images

June 29 - Comment - Like - Share

I think it's based on this paper: http://murphylab.web.cmu.edu/publica... - Michael Kuhn

Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed... - Michael Kuhn

Allyson Lister

SIG: DAM and BOSC Joint Session: BioHDF: Open binary file formats for large-scale data management, Mark Welsh, geospiza.com

June 27 - Comment - Like - Share

Cass Johnston and Tom Walsh liked this

...aka Toward Scalable Bioinformatics Infrastructures - Allyson Lister

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@Allyson: Thanks for setting up all those talk threads! - Oliver Hofmann

Ouch: "Byte-ing off more than you can chew"!! - Allyson Lister

HDF5 is a model and file format for large complex data: http://www.hdfgroup.org/HDF5... - Brad Chapman

@Oliver - no problem - I just check before posting that someone hasn't done it before me :D - Allyson Lister

Allyson -- seconded. Great work. Nice to have others here. I refuse to comment on that pun-filled slide. - Brad Chapman

Problem: handling mutiple next-gen sequencing data while still being able to drill down to the original sequence reads. Aim is to generate domain-specific HDF5 extensions to move away from a flat-file format. - Oliver Hofmann

@Brad - it's definitely more fun to liveblog in a community of bloggers :) - Allyson Lister

HDF5 is a fairly complicated API. BioHDF layers a biology oriented interface on top of it, targeted at next generation sequencing especially. Appears to sit on top of one or more HDF databases. Having trouble finding the code itself. Geospiza BioHDF page is here: http://www.geospiza.com/researc... - Brad Chapman

I wonder when the time is right to start referring to "current-gen sequencing", soon we'll have to start saying "next-next-gen" when talking about single-molecule sequencing. - Andy Jenkinson

The BioHDF page seems to be here: http://hdfgroup.com/project... Edit: Nevermind, that link resolves to the HDF front page... - Oliver Hofmann

He has a bagful of thumb drives with the HDF software pre-loaded. good idea! - Allyson Lister

@Andy - very funny :) I know people who, similarly, hate to hear the phrase "post-genomic era"! - Allyson Lister

Do we get to keep the drives :) ? - Oliver Hofmann

Aha, here is the page: http://www.hdfgroup.org/project... - Brad Chapman

Blog Post: http://themindwobbles.wordpress.com/2009... - Allyson Lister

plug for piotr's talk in the BIo* update session tomorrow - Jim Procter

I'm still confused. Hierarchical data. Random access to the data. Is this not a file system? Why not use a filesystem? - Phil Lord

Allyson — thanks for blogging my talk at BOSC / ISMB. And, I'm afraid we're already using the term "next-next-gen" to describe technologies like those of Helicos or Oxford Nanopore. - Mark Welsh

Ah, the pun-filled slide... in my defense, those were other peoples' puns; however, I'm guilty of propagating them (anything for a laugh in a technology talk). - Mark Welsh

You can download the current BioHDF prototype software from the "BioHDF Command Line Tools" link here: http://www.hdfgroup.org/project... - Mark Welsh

The BioHDF slides are available here on slideshare (along with all the other talks from the conference): http://www.slideshare.net/bosc... - Mark Welsh

There will be a scivee.tv presentation of our ISMB poster also — looks like its not up yet though. - Mark Welsh

HDF is kind of like a file system within a single binary file. However, those "files" (called datasets in HDF) are multi-dimensional arrays with each element being an arbitrarily complex data structure. - Mark Welsh

@Mark - thanks for the extra information and comments. It's always good to be able to go back and look over the slides. :) - Allyson Lister

Ruchira S. Datta to ISMB/ECCB Stockholm 2009, The Life Scientists

Now posting at the Quest for Orthologs here: http://friendfeed.com/questfo...

July 3 - Comment - Like - Share

Abhishek Tiwari and Peter Menzel liked this

That has a private feed, Ruchira :) - Allyson Lister

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Sorry, I fixed it. - Ruchira S. Datta

Perhaps I'm not refreshing properly, but it still seems to be private :) - Allyson Lister

Oops, hopefully fixed it for real this time. Sorry! - Ruchira S. Datta

works fine now.. thanks for blogging this! - Peter Menzel

I was just requested to hide the feed, so it's now private again and will remain private. - Ruchira S. Datta

Ok - no worries! - Allyson Lister

Hedi Hegyi

we couldn't get in to the party either - so we went to the Bishop's Arms - a lively English pub on Vasagatan - about 100m from Sheraton where the party was held. No music, thanks God, so we were able to carry on meaningful conversations. I spotted these folks outside the Sheraton party :-)

July 4 - Comment - Like - Share

Allyson Lister

ISMB Light Factory: Party on Wednesday night open thread

July 1 - Comment - Like - Share

Left the party relatively early to allow the long queues outside to move into the party (at least by one person!). had fun - thanks to the organizers - Allyson Lister

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yes, thanks to the organizers - Ruchira S. Datta

there is no dancing at math conferences - Ruchira S. Datta

now you know why i'm in bioinformatics ;-) - Ruchira S. Datta

@Ruchira - very good point! - Allyson Lister

Yeah, you need to reserve some time for the coverage! :) - Egon Willighagen

deeply disappointed that nobody live-blogged the party - I had expected real-time updated playlist and more ;) - Lars Juhl Jensen

Would be fun :) Seeing the comments become more non-sense as the commenter gets drunk... - Egon Willighagen

Well, about the playlist: Good tracks included James Brown, various reggae stuff, and Tainted Love :) - Allyson Lister

wished the venue would have been bigger so everyone could get in. - David Sexton

did y'all hear about the thief? took someone's backpack, someone's purse, and someone's camera. owner of the backpack noticed it was missing, walked outside and saw this guy with an enormous backpack. when he called to the guy, the guy ran. it was the same guy who was bothering a lot of women earlier (in one case, took her purse). i was so annoyed by him getting in my face that i left--so my things are safe, luckily for me! heard all this from the owner of the backpack at the services desk. - Ruchira S. Datta

@David I don't think that they thought so many would attend :) Victim of its own success? - Allyson Lister

@Ruchira - that's awful! I'm really glad I put my bag in a locker. So, a few people have descriptions of him? And does that mean he was a conference attendee, or just gate-crashed? Yikes... - Allyson Lister

@Allyson, I expect so. You may have noticed him at some point--short, dark complexion. I hadn't seen him before the party, but that doesn't mean anything. I was asked only "CS or bio?" at the door, but I had my badge on. - Ruchira S. Datta

Hey guys, Allyson is correct. Based on last year's party, we expected far fewer people to come. For everyone who came and could not get in initially and had to wait or got frustrated and left -- we are really sorry. It is a priority for next year to make sure that doesn't happen again. Regarding the thief, we believe he snuck in aided by a couple of friends who distracted the security.... more... - Dave Messina

Lars Juhl Jensen

Wordle contributors cloud v3 - now weighted by comment length

July 3 - Comment - Like - Share

Mike Chelen, Gabriele Sales, Nakao M. and 2 other people liked this

As *demanded* by Roland Krause - but it is not corrected for mean attendance, complexity of the presented material, and smileys. Nor did I include the many excellent blog posts from Allyson and Oliver in the counts. These improvements are left as an exercise for the reader ;-) - Lars Juhl Jensen

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ok, now what other obscure references can we make Lars process :) - split by day, then morning or afternoon sessions - we can infer who was networking into the night, if they are all comments on afternoon sessions :), then by star sign of the presenters :) - Frank

@Lars, constantly amazed by how much you get done on the side ;) thanks! - Oliver Hofmann from iPhone

Yes, I'd like to add my thanks - fantastic! :) - Allyson Lister

Thanks a lot Lars! Now you can apply machine learning to infer what areas the different FFers are interested in... ;-) - Ruchira S. Datta

Or I could just take the old-fashioned approach and read what you all wrote ;-) - Lars Juhl Jensen

Lars Juhl Jensen

Thanks to everyone for all the live commentary! In return, I give you a Wordle cloud based on all the comments that were posted in this room :-)

July 2 - Comment - Like - Share

Eleni Mikroyannidi, Frank, Piotr Byzia and 15 other people liked this

Surprised 'Allyson' is not one of the large keywords :) - Oliver Hofmann from iPhone

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I used only the comments themselves - not the names of the people who posted them - Lars Juhl Jensen

Maybe make a Wordle out of the contributors? - Cameron Neylon

Did someone spot the 'Open' yet? - Egon Willighagen

Cameron, contributors cloud done and posted :) - Lars Juhl Jensen

I see a homologous word in the two Wordles! Latin data = Sanskrit datta, "given". :-) - Ruchira S. Datta

@Oliver - to answer your question there are a number of "@" names in the wordle, if you look closely, but yeah, it's very nice of @Lars to do both wordles! I can see @allyson and @oliver for instance - Allyson Lister

Looks like we should ramp up our vocabulary of verbs - use, using and used are all prominent items by themselves. - Roland Krause

I'm amazed by the difference between the Wordle based on abstracts (http://larsjuhljensen.tumblr.com/post...) and this one. The abstracts seem to focus on methods whereas the FriendFeed comments focus on data. - Lars Juhl Jensen

At least partially because it is much easier to quickly describes test data set than a complex method that might require notation or a schema, I think - Oliver Hofmann from iPhone

Lars Juhl Jensen

Wordle contributors cloud v2 (now with first and last names concatenated)

July 2 - Comment - Like - Share

Allyson Lister, Nakao M., Venkata P. Satagopam and 9 other people liked this

Ally comes in at a suprising second by my eyes! - Frank

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Apologies to those of you with foreign characters in your names, which got mangled by Wordle :-/ - Lars Juhl Jensen

you can use a tilde to keep words together but maintain the space http://www.wordle.net/faq#spa... - Simon Cockell

Frank, me too! I wonder if this Wordle excluded the non talk specific things (e.g., FF shut us down) - Ruchira S. Datta

No it was just a quick'n'dirty hack: download all comments as JSON in batches of 30 topics, extract FriendFeed user names, paste into Wordle, submit to FriendFeed ;-) - Lars Juhl Jensen

Now you know how to order the authors when you write up the meeting :-) - Neil Saunders

well, that would probably explain it then :-) - Ruchira S. Datta

I don't think so Ruchira - the distance from Ally to you is more than 150 comments. I doubt you made *that* many non-talk comments (but I haven't checked). - Lars Juhl Jensen

Simon, thanks - I won't pester people with a v3 of this cloud, though ;-) - Lars Juhl Jensen

Think Allyson (and to some extent I) switched to the blog posts and stopped pasting over comments to ff when coverage was already good -- and Ruchira, your coverage was fast and incredibly thorough :) - Oliver Hofmann

I demand that the analysis is normalized by comment length! And mean attendance! And complexity of the presented material! And smileys! - Roland Krause

@Roland you are very funny! If you want to know my hypotheses, then: @Ruchira should be first for FF comments, as she definitely ramped up her commenting over the week, even including the SIG comments (which I guess were included :)); also, as @Oliver says, both of us mainly switched to blog posts as the week went on, especially for talks where other FFers were about. I'm not demanding that Lars re-write to pull down word counts from comments or blog posts, though :) (But it would be interesting! :D) - Allyson Lister

ISMB/ECCB

Keynote: Webb Miller - Bioinformatics Methods to Study Species Extinctions

July 1 - Comment - Like - Share

Allyson Lister, Dawn, Reinhard Schneider and 2 other people liked this

10 Steps to Success in Bioinformatics - sebi

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has been 40 yrs in computers, 20 yrs in bioinformatics: but doesn't have enough money to retire (tongue-in-cheek) - Michael Kuhn

Step 1: Become a biologist. - sebi

http://www.iscb.org/index... - Peter Menzel

extinction - Venkata P. Satagopam

Extinction: How to save endangered species - Peter Menzel

which species are in trouble? - Venkata P. Satagopam

Here's the article "10 steps to success..." http://www.iscb.org/iscb-pu... - Michael Kuhn

3 stories - Venkata P. Satagopam

(out of batteries, not sure the iPhone is adequate for this. So far a great intro :) ) - Oliver Hofmann from iPhone

3 studies: Tasmanian tiger, Mammoth, ... - Peter Menzel

explains how DNA can be found in hairs. - Peter Menzel

For extinct species, mitochondrial genome is easier to sequence, as it is up to 1,000 times more abundant than genomic DNA - sebi

aDNA = ancient DNA - Peter Menzel

background of ancient DNA ... - Venkata P. Satagopam

what can be learned from aDNA? - Venkata P. Satagopam

1. phylogenetics - Peter Menzel

2. population genetics - Peter Menzel

This has some parallels to the last talk in today's session in T1 by RE Green: Neandertal mitochondrial DNA to place them (and us) in the phylogenetic tree - sebi

3. directly observe evolutionary rates - Peter Menzel

genes - Venkata P. Satagopam

4. observe evolution of function - Peter Menzel

short reads are good enough for aDNA junks - Peter Menzel

next-generation seq of aDNA - Venkata P. Satagopam

aDNA from hairs can easily be decontaminated - Peter Menzel

aDNA from hair shafts enclosed in a plastic bag like .... - Venkata P. Satagopam

Tasmanian tiger: extinction date 7/9/1936 - Peter Menzel

over 700 know specimens - Venkata P. Satagopam

http://thylacine.psu.edu - Peter Menzel

thylacine = tasmanian tiger - Peter Menzel

attempts to study thylacine DNA - Venkata P. Satagopam

observations - Venkata P. Satagopam

2 mitochindrial genomes in GenBank - Peter Menzel

in GenBank two genes 12S, cytb both were wrong - Venkata P. Satagopam

both wrong at 10% of nucleotides - Peter Menzel

tasmanian devil closest relative to tiger - Peter Menzel

split at ~40m years ago - Peter Menzel

30% of new sequence data are from nuclear genome - Peter Menzel

-> maybe sequence whole genome? - Peter Menzel

one imp question ... did an epidemic contribute to extinction? - Venkata P. Satagopam

Epidemic probable cause of extinction - Peter Menzel

(the quiet comments are hillarious. 'we sequenced one from Stockholm swimming in alcohol. Long way from home, extinct, drowning his sorrows...') - Oliver Hofmann from iPhone

story 2 wooly mammoth - Venkata P. Satagopam

Mammoth: - Peter Menzel

hair sample from eBay - Peter Menzel

we found sample on ebay - Venkata P. Satagopam

for 90$ :-) - Peter Menzel

most samples are from Sibiria - Peter Menzel

have now 18 different complete mtDNA sequences - Peter Menzel

what we draw from this analysis ....mammoth separated from living elephants 6m years ago - Venkata P. Satagopam

like chimp and human - Peter Menzel

want to sequence the full nuclear genome - Peter Menzel

already got 0.7-fold coverage - Peter Menzel

= 3.3 billion bp - Peter Menzel

assuming real size of genome is 4.7Gb - Venkata P. Satagopam

aa identitiy is nearly 99.8% between mammoth and elephant - Peter Menzel

99.4% overall nucleotide identity - Peter Menzel

This equals 1 mutation per protein - sebi

(all this excluding indels) - Peter Menzel

90% seq from the sample from the wooly mammoth - Venkata P. Satagopam

Mammoths differ from all other vertebrates in some highly conversed genes, such as MRTO - Venkata P. Satagopam

maybe due to living in cold places - Peter Menzel

extinction scenario ...human killed them all - Venkata P. Satagopam

certainly not - Venkata P. Satagopam

extinction szenario: killed by humans.. become to warm... -> but thats' not true - Peter Menzel

humans arrives to late in Siberia - Peter Menzel

3rd story Tasmanian devil - Venkata P. Satagopam

tasmanian devil now - Peter Menzel

threatened by extinction due to cancer - Peter Menzel

cancer cells passed around by biting each other - Peter Menzel

cancer is passed through infection (biting other individuals, spreading cancer cells) - sebi

some resistant individuals - sebi

Trying to preserve the species, keeping the gene pool large enough - sebi

compared two individuals: one who is resistant, one who died - Peter Menzel

Finding out about the resistance: considering an ortholog of a human tumor supressor gene - sebi

the guy who died, has a mutation at an extremely conserved position - Peter Menzel

but not much is known what it means.. - Peter Menzel

want to look at non-coding nuclear SNPs - Peter Menzel

closest sequenced relative is oppossum - Peter Menzel

90m years of separation - Peter Menzel

-> computational problem: SNPs without a reference genome - Peter Menzel

produce sequences from many individuals instead - Peter Menzel

and compare SNPs there - Peter Menzel

-> extract population structure - Peter Menzel

seems to work.. but no final data... - Peter Menzel

Quick summary: Bioinformatics very helpful, but much more data needed - Peter Menzel

Role of genetic diversity in extinction still not really known.. no simple story - Peter Menzel

but genetic diversity not necessary a good indicator for risk of extinction.. - Peter Menzel

e.g. panda has high diversity, but endangered - Peter Menzel

TV documentary from Australia: http://www.abc.net.au/catalys... - Peter Menzel

(only to get the blog on top of the ISCB portal site; the figures messed up our layout) - Reinhard Schneider

Related: 11 Extinct Animals That Have Been Photographed Alive: http://ecoworldly.com/2009... - Peter Menzel

ISMB/ECCB

HL58: Caroline Friedel - A new method for high-resolution gene expression analysis

July 1 - Comment - Like - Share

Diego M. Riaño-Pachón liked this

Metabolic tagging of newly transcribed RNA - Diego M. Riaño-Pachón

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Able to measure decay and de novo synthesis - Diego M. Riaño-Pachón

this methods tries to solve a long standing problem in transcriptomics, ] - Diego M. Riaño-Pachón

i.e., bias for differential expression of short-lived RNAs - Diego M. Riaño-Pachón

and thus in subsequent analysis - Diego M. Riaño-Pachón

solution is to perform gene expression analysis of newly transcribed RNA - Diego M. Riaño-Pachón

using 4-thiouridine - Diego M. Riaño-Pachón

Kenzelmann et al PNAS 2007 http://www.ncbi.nlm.nih.gov/pubmed... - Diego M. Riaño-Pachón

after tagging,normal analysis techniques for microarray or RNA-seq can be sused - Diego M. Riaño-Pachón

bur of course new methods could exploit features specific for the tagging of newly transcribed RNA - Diego M. Riaño-Pachón

directly observe changes in de novo transscription - Diego M. Riaño-Pachón

observe changes relative to basal transcription - Diego M. Riaño-Pachón

no bias for short-lived trnascripts - Diego M. Riaño-Pachón

It can offer evidence of the stability of RNA (decay) - Diego M. Riaño-Pachón

(room pretty full) - Diego M. Riaño-Pachón

New methods for normalization are necessary when comparing total RNA to newly transcribed RNA - Diego M. Riaño-Pachón

after normalization the RNA half-life can be calculated using and exponential decay model - Diego M. Riaño-Pachón

the exp. technique with the new normalization increases the precision on the estimation of RNA half-life - Diego M. Riaño-Pachón

Friedel et al, 2009 NAR; http://www.ncbi.nlm.nih.gov/pubmed... - Diego M. Riaño-Pachón

Q: is 4-thiouridine toxic to the cell? A: No, at least in the time points looked at. - Diego M. Riaño-Pachón

http://www.ncbi.nlm.nih.gov/pubmed... - Diego M. Riaño-Pachón

Q: is there a bias towards transcript length? A: They did not see any significant correlation - Diego M. Riaño-Pachón

(only to get the blog on top of the ISCB portal site; the figures messed up our layout) - Reinhard Schneider

ISMB/ECCB

HL57: Erik Sonnhammer - FunCoup: global networks of functional coupling in eukaryotes

July 1 - Comment - Like - Share

How to reconstruct networks - experimental networks are incomplete. - Roland Krause

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Up to 300.000 interactions are proposed for human - Roland Krause

only 35000 known - Ruchira S. Datta

Each experimental method can give you more than 20% of the interactions. - Roland Krause

experiments have high false negative and false positive rates - Ruchira S. Datta

e.g., false positives from in vitro experiments: the interaction may never happen in a living cell - Ruchira S. Datta

Interactions have to be combined and evaluated. - Roland Krause

FunCoup - Venkata P. Satagopam

there are many kinds of evidence for functional coupling - Ruchira S. Datta

Lots of evidence for functional coupling, not only from PPI but als from localization, gene expresson, interacting domain, TFBS; miRNAs. - Roland Krause

domain interactions - Venkata P. Satagopam

See also http://ff.im/4xrCV - Ruchira S. Datta

Integrate different kind of data from various organisms. - Roland Krause

Some links are continous, some binary, etc. - Roland Krause

using Naive bayesian training - Venkata P. Satagopam

full Bayesian training would be too computationally heavy - Ruchira S. Datta

Naive Bayesian training, going from continuous data to distinct bins. - Roland Krause

compare with positive and negative reference datasets - Ruchira S. Datta

There is no negative reference data set out there, genes in different compartment might actually interact. - Roland Krause

therefore use random examples as negative set - Ruchira S. Datta

calculate enrichment as likelihood ratio=P(+)/P(-) - Venkata P. Satagopam

Learn log likelihoiod ratios for each evidence, requires large negative set. - Roland Krause

sum all the log-likelihood ratios to get full bayesian score - Ruchira S. Datta

4 different flavors of training sets: metabolic pathway, signaling pathway, physical ppi, and complexes from UniProt - Ruchira S. Datta

Training sets are from KEGG (metabolic and signaling), HPRD and Complexes from Uniprot. - Roland Krause

using the curated data only for training/validation, not as input to the networks - Ruchira S. Datta

No curated data used in the network, only in training. - Roland Krause

7 model organisms and human are combined with 50 individual data sets. - Roland Krause

Convert log scores to confidence scores. - Roland Krause

predict coupling between 2 genes, for each model FC-PI, FC-CM, FC-ML, FC-SL model - Venkata P. Satagopam

convert into confidence scores, which may be different in different models - Ruchira S. Datta

convert the Bayesian score using the probabilitly of functional coupling, which is unknown but they just set to 1/1000 ad hoc - Ruchira S. Datta

algorithmic innovations- we have to develop new evidence scores - Venkata P. Satagopam

Used input from PPI as continuous data, using experimental counts. - Roland Krause

discretization caused problems - Ruchira S. Datta

they figured out how to discretize - Ruchira S. Datta

test significance with chi-squared test - Ruchira S. Datta

integrate evidence from orthologs used by InParanoid - Ruchira S. Datta

using inparanoid orthologs - Venkata P. Satagopam

Used transfer of ortholougs information under the same Bayesian framework - Roland Krause

new phylogenetic patterns using orthologs - Ruchira S. Datta

http://inparanoid.sbc.su.se/ - Venkata P. Satagopam

Except for yeast, most species had more information transferred rather than generated for the organism. - Roland Krause

most support coming other species, other wise we may miss - Venkata P. Satagopam

many links would not have been found without evidence from other species - Ruchira S. Datta

only yeast is well supported all by itself - Ruchira S. Datta

validated networks, TCGARN science 2008 - Venkata P. Satagopam

Validation using cancer pathways, recovering 29 of 36 links, found an additional 25. Not entirely independent. - Roland Krause

Independent validation from recovering tumour mutation sets. - Roland Krause

applications - 1 . exploring local networks, 2. analyzing network conservation - Venkata P. Satagopam

3? - Venkata P. Satagopam

Easy exploration of the data sources leading to an edge in the network. - Roland Krause

graph visualization: started with Medusa, but it didn't fulfill needs - Ruchira S. Datta

now developed JSquid (sp?), published last year - Ruchira S. Datta

used jSquid .. Bioinformatics 2008 - Venkata P. Satagopam

New view of the human disease network, build tree of disease interactions. - Roland Krause

conclusions - Venkata P. Satagopam

to discover novel functional coupling between genes - Venkata P. Satagopam

Cancers group together, neurological diseases do not. - Roland Krause

can expand gene sets such as pathways - Venkata P. Satagopam

http://FunCoup.sbc.su.se - Venkata P. Satagopam

(only to get the blog on top of the ISCB portal site; the figures messed up our layout) - Reinhard Schneider

ISMB/ECCB

HL61: Lee Newberg - Global Measures of Uncertainty: Long Overdue in Computational Molecular Biology

July 1 - Comment - Like - Share

Neil Saunders liked this

two papers: webb-robertson & lawrence; newberg ... lawrence - Michael Kuhn

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what is a good e-value? - Diego M. Riaño-Pachón

E- and p-values are small when random data in unlikely to do well - Michael Kuhn

E-values and p-values tell you about random data but not whether there are other solutions. - Roland Krause

but there still might be other solutions which equally good E or p values - Michael Kuhn

need to define confidence / credibility limits - Michael Kuhn

e-values and p-values are poor proxies to credibility - Diego M. Riaño-Pachón

an example from RNA 2D prediction, MFE is not the best representative - Diego M. Riaño-Pachón

today's goal: compute a global measure of representativeness of a point estimate - Michael Kuhn

solution spaces are immense, but we often choose a particular point estimate... misleading e.g. if there's a bimodal solution - Michael Kuhn

Goal: Compute global mesaure of representativeness of a point estimate - Peter Menzel

Many problems are tackled by dynamic programming, HMMS, etc, collectively they are Hidden Boltzmann Models - Roland Krause

compute / estimate credibility: look at distribution of differences from point estimate - Michael Kuhn

SW alignment of nt sequences, score distribution can be modeled by exponential distribution. For a 3000x3000 alignment, the Fourier approach is fast. - Roland Krause

Will not explain all about Fourier Transform (in 15 minutes). - Roland Krause

use the credibility limit, is a simple number, even a biologist can understand that - Diego M. Riaño-Pachón

Author: http://www.rpi.edu/~newbel/ - Diego M. Riaño-Pachón

(only to get the blog on top of the ISCB portal site; the figures messed up our layout) - Reinhard Schneider

ISMB/ECCB

HL62: Richard Green - A Complete Neandertal Mitochondrial Genome Sequence Determined by High-Throughput Sequencing

July 1 - Comment - Like - Share

Allyson Lister and sebi liked this

Neandertals: closest extinct relative. existed 400000-30000 yrs ago - Marcel Martin

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chimps are closest living relatives, but deviated longer ago - Marcel Martin

first DNA from extinct species was in 1985 from the Quagga - Marcel Martin

Neandertal mitochondrial genome, as it is present about 1000 copies per cell vs 2 copies of genomic DNA - sebi

mitochondrial genome is easier to recover since there are many copies per cell - Marcel Martin

http://www.mitomap.org/WorldMi... - Marcel Martin

Mitochondial genome is useful for tracking maternal lineages, and it accumulates mutations slowly -- ideal for building trees - sebi

seems like there was no interbreeding between Neandertals and modern humans - Marcel Martin

Deep sequencing with high-throughput next generation sequencing, used to be direct PCR - sebi

ancient DNA fragments are just 60nt in length - Marcel Martin

Roche/454 and Illumina sequencing was used, no need to fragment DNA (more fragmented than one would like anyway) - Marcel Martin

many C to T transitions, also G to A - Marcel Martin

COX2 protein has 5 differences between chimp and human, 4 of 5 differences happened in the last 600,000 yrs, so Neandertals also have 4 different AAs compared to Homo sapiens - sebi

Maybe fast evolving sites? Reverting to previous (=monkey), more advantageous AAs? - sebi

sequencing errors: 3% of all Cs are Ts, same for G->A. Reason: C is deaminated to U, then seen as T - Marcel Martin

higher probability for deamination at the end of fragments. Perhaps because cytosine deamination is 100x faster in single-stranded DNA and end of fragments are single-stranded - Marcel Martin

MIA: mapping iterative assembler. manuscript in preparation - Marcel Martin

Measuring protein evolution with a ratio of non-synonymous differences to synonymous differences dN/dS: indicative of a small Neandertal population size - sebi

(only to get the blog on top of the ISCB portal site; the figures messed up our layout) - Reinhard Schneider

ISMB/ECCB

Keynote: Mathias Uhlen - A global view on protein expression based on the Human Protein Atlas

July 1 - Comment - Like - Share

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Introduction: Works a lot on affinity reagents. Invented and developed pyrosequencing technology (http://en.wikipedia.org/wiki...) now used in 454 - Allyson Lister

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Out line of the talk - 1. systematic biology -introduction, 2. HPR project 3. The Human protein Atlas - Venkata P. Satagopam

18th century - biologist. 19th - chemist (1/3 of elements discovered in Sweden in this century). 20th - physicists and at the end, computer scientist. He'd now like to say that the 21st century is the century of medicine. - Allyson Lister

HPR one of the largest projects in Sweden wrt funding, about 100 million euro so far - Oliver Hofmann

An impressive log-scale plot of number of bases sequenced since 1965. - Allyson Lister

developer of sequencing by synthesis via pyrosequencing in late 90s -- basis of 454 technology - Andrew Su

Personalized genomics ... 454 technology developed in our lab - Venkata P. Satagopam

Bioinformatics is the key in the new era of genomics. - Allyson Lister

95% of drugs (still) aimed at proteins - Oliver Hofmann

(Personal opinion: I like how it's not the "post-genomic era", but a new era of genomics :) ) - Allyson Lister

95% of drugs today target proteins. Thus, studying proteins is studying for the future - Diego M. Riaño-Pachón

Systems biology /omics is going to be fantastic in the next 10 years. - Allyson Lister

(That, or we find better ways of interfering with RNA) - Oliver Hofmann

Image of contradictory sign in Paris: you know where you want to go, but not how to get there. - Allyson Lister

We know where we want to go (characterize all proteins), but not sure how to get there (due to a lack of high-throughput methods) - Oliver Hofmann

The generation game - Nature july 7, 2007 - Venkata P. Satagopam

antibodies are the core tool for probing proteins - Andrew Su

but they are too cross-reactive - Diego M. Riaño-Pachón

Human antibody initiative HAI - Venkata P. Satagopam

human anitobdy initiative (HAI) -- uhlen, M. Synyder, P. Hudson -- generate comprehensive and validated antibody collection - Andrew Su

validation of commercially available antibodies - Venkata P. Satagopam

average success rate of commercial antibodies is 49% - Andrew Su

some companies 100% antibodies works fine, some companies 0%, in general 50% works fine - Venkata P. Satagopam

http://www.antibodypedia.org/ - Oliver Hofmann

Antibodypedia -- a portal for validated anitbodies (we need to add a link from Gene Wiki...) - Andrew Su

From the website: "The antibodypedia is a community-based portal showing application-specific validation of publicly available antibodies to human protein targets. Each protein binder (antibody or other affinity reagent) has been scored in an application-specific manner into three main categories (supportive, uncertain and non-supportive)" - Oliver Hofmann

@Oliver - nice! - Allyson Lister

If you have 2 antibodies, you can compare results in various assay platforms so he wants to develop paired antibodies for every protein target. - Allyson Lister

Nat Methods 2008: High-througput method to identify epitopes - Oliver Hofmann

6 months ago published a paper Nature methods (december 2008) - Venkata P. Satagopam

(bummer, antibodypedia doesn't use mediawiki so can't assess current usage...) - Andrew Su

(I am entirely too short-sighted to read the author lists half of the time. Sigh) - Oliver Hofmann

HPR - The human proteome resource - Venkata P. Satagopam

http://www.proteinatlas.org/ - Oliver Hofmann

(grumble grumble, antibodypedia creates YAI -- yet another identifier) - Andrew Su

(++ HPA -- uses ensembl gene IDs...) - Andrew Su

hpr is a multi-disciplinary program - Venkata P. Satagopam

(Proteinatlas seems to be using ENSG/ENSP/UniProt) - Oliver Hofmann

The gene factory does about 200 clones per week, and is in full production. - Allyson Lister

(HPA ids- mapped to uniprot also) - Venkata P. Satagopam

Close to 34.000 clones in the database - Oliver Hofmann

(@Andrew - indeed) - Allyson Lister

200 clones per week, 33,925 clones total (all human?) - Andrew Su

Open source (but in-house?) LIMS developed - Oliver Hofmann

(would be interesting to compare to origene collection of mammlian clones) - Andrew Su

The antigen design uses PRESTIGE, which is a bioinformatics approach to select antigens using the protein epitope signature tag (PrEST). - Allyson Lister

antigen design -- used PRESTIGE a bioinformatics approach to select antigen for antibody - Venkata P. Satagopam

read of this project is protein expression profiling - Venkata P. Satagopam

readouts -- immunohistochemistry (IHC) and IF (immunofluorescence) - Andrew Su

Organ, tissue, cellular and sub-cellular expression profiing on a protein basis - Oliver Hofmann

apply antibodies to tissue arrays (cancer focus, I think) - Andrew Su

(140+ human samples, around 200 tissues.. did someone catch the numbers?) - Oliver Hofmann

(Faq from the website: spatial distribution of proteins in 48 different normal tissues and 20 different cancer types as well as 47 different human cell line) - Oliver Hofmann

annotation of images taking place in Mumbai in India - Venkata P. Satagopam

image annotation -- difficult problem. automated anaylsis would be good, but now using indian pathologists for manual annotation - Andrew Su

$60 / 500 images for annotation? - Andrew Su

Confocal microscopy for subcellular localization, difficult to scale up to high-throughput - Oliver Hofmann

high-throughput subcellular localization in A0431 (squamous cell carcinoma), U-251MG (glioma), ??? - Andrew Su

(I think Bob Murphy talked on a similar project to map subcellular localization of proteins en masse...) (Oh, looks like it's a collaboration between the two...) - Andrew Su

They have a SVM that seems to be able to annotate 28 different parts of the cell. - Allyson Lister

2TB data each week (courtesy of 50.000 images in the same time) - Oliver Hofmann

2/3 of data come from in house data and 1/3 comes from different companies - Venkata P. Satagopam

(I wonder how the protein expression compares with our gene expression atlas http://www.ncbi.nlm.nih.gov/pubmed...) - Andrew Su

About 33% of the sample space done (6850 genes) - Oliver Hofmann

Any mention of the Teasdale lab in Queensland? They do a lot of good subcellular classification work; SVMs, fluorescence microscopy. Try "Teasdale R[au]", PubMed. - Neil Saunders

progress - started in 2005 , last week released version 5. 8,832 antibodies, covering 1/3 genes in uniprot - Venkata P. Satagopam

(And I suppose there's always more to do.. check for splice variants, truncated versions...) - Oliver Hofmann

Most recent release: 7 mln images. - Allyson Lister

(@Andrew: if there is overlap in the cell lines that could be an easy correlation analysis) - Oliver Hofmann

The next 5 yrs are also about getting the paired antibodies mentioned earlier. - Allyson Lister

all antibodies available to the public - Venkata P. Satagopam

(good good, HPA is already BioGPS plugin.. http://biogps.gnf.org/#goto=p... </shameless_plug>) - Andrew Su

Rodent brain atlas at http://hprdemo.genpat.uu.se/rodentb... - Oliver Hofmann

central questions in proteomics - Venkata P. Satagopam

(Rodent atlas seems a bit redundant to Allen Brain Atlas? -- Oh, ABA is via in situ / RNA, this is protein. Again, would be interesting to compare...) - Andrew Su

how many proteins are expressed in a given cell? - Venkata P. Satagopam

how many protein are tissue specific? - Venkata P. Satagopam

@Oliver, probably not directly comparable by exact cell lines, but might be worth comparing by parental tissue. Need to wait until they allow downloading of data though... - Andrew Su

Ensembl "thinks" that the genes are up to 23,000, but UniProt "thinks" 20,000, but the number is probably with that (for genes coding for proteins). ("thinks" in scare quotes, as databases don't think - yet) - Allyson Lister

the size of human membrane proteome .. 5,514 human membrane proteins; covering 26% of protein-encoded genes - Venkata P. Satagopam

proteins expressed in normal cells - 6,800 antibodies towards (>25% of all protein encoding genes). 65 normal cell types (from 45 different tissue types) - Venkata P. Satagopam

70% of proteins expressed in a given cell, approx even distribution across # of cell lines (not what we observed on gene expression data, which had distinct peaks at tissue-specfiic and ubiquitous) - Andrew Su

80% of proteins expressed on average in cell lines (surprisingly high to me...) - Andrew Su

(@Andrew: protein selection might be biased towards the ones that are well expressed / had known anitbodies / ...) - Oliver Hofmann

9% of proteins cell type specific, 62% expressed across 3 different cell types - Oliver Hofmann

ubiquitous expression, but differing levels - Andrew Su

(interesting cytoscape visualizations of cell type / tissue specificity) - Andrew Su

In the Atlas: < 2% specific to a single cell type (84 proteins), well known ones like insulin - Oliver Hofmann

Includes a number of uncharacterized proteins with no known function - Oliver Hofmann

EU project http://www.prospects-fp7.eu/ - Oliver Hofmann

PROSPECTS: PROteomics SPECification in Time and Space - Allyson Lister

"Complementary technologies, including mass spectrometry, cryoelectron microscopy and cell imaging will be applied in innovative ways to capture transient protein complexes and the spatial and temporal dimensions of entire proteomes." - Oliver Hofmann

MCF-7 data with IHC, Mass spec - Oliver Hofmann

next generation seq of cDNAs from U2-OS human cell line 76% detected by mRNA seq - Venkata P. Satagopam

76% genes detected by next gen mRNA sequencing in U2-OS - Andrew Su

again -- mostly ubiquitous expression (now on mRNA level), but differing levels - Andrew Su

high fractions of all proteins expressed in human cells, tissues and organs - Venkata P. Satagopam

Lack of specificity not good knows for those looking for good antibody targets for therapeutic purposes - Oliver Hofmann

the quantity of proteins, rather than their presence /absence, is the key to cell identity - Diego M. Riaño-Pachón

few cell-specific proteins (<1%) and group-specific proteins (<10%) - Venkata P. Satagopam

find biomarkers for early detection of disease ... it is very good for human mankind - Venkata P. Satagopam

(Proteome 2008) Suspension bead arrays - Oliver Hofmann

mg/ml to pg/ml range (dynamic range of protein concentration in blood 10^12 ) - Oliver Hofmann

working on kidney disease in collaboration with astrazanica .... for detection of biomarkers - Venkata P. Satagopam

Developing 'next generation' plasma profiling, scale to one million assays / months - Oliver Hofmann

(has he mentioned availability of these antibodies? Commercially available? antibody-producing lines?) - Andrew Su

They're part of ENGAGE. - Allyson Lister

commercially available @Andrew - Allyson Lister

first draft of the human proteome by 2014 - Venkata P. Satagopam

Aim to have the draft version of the human proteome by... see above - Oliver Hofmann

(@Andrew I think via Prestige Antibodies (I remember the cute advertising slide). Does that mean advertising works?) - Allyson Lister

Nature, "The big ome" - 24 April 2008, editorial - Allyson Lister

tissue-specificity is achieved by precise regulation of protein levels in space and time - Venkata P. Satagopam

Prestige Antibodies through Sigma: http://www.sigmaaldrich.com/life-sc... - Andrew Su

science 26 sep 2008, vol 321 pages 1758-1761 - Venkata P. Satagopam

"Proteomics Ponders Prime Time", Science, 26 September 2008, in response to the Nature article - Allyson Lister

new lab in Stockholm coming soon, Science for Life Laboratory - Venkata P. Satagopam

Blog post: http://themindwobbles.wordpress.com/2009... - Allyson Lister

New Science for Life laboratory being established, see http://www.newsdesk.se/pressro... - Oliver Hofmann

Q: importance of splice isoforms -- A: complexity that is currently not considered due to technical complexity (to be saved for second phase) - Andrew Su

Q: conclusions on tissue specificity have bias based on antibody availability? A: bias of commercial antibodies possible, but only 1/3 of data. Data they are generating based on walking down chromosomes (I think?), so don't expect bias... Also, some of ubiquitous expression is due to cross-reactivity. (first mention of this...) - Andrew Su

Q: perspective for gene therapy or antisense therapy, more generally non-protein based therapies. A: pharma shifting from small molecules to biologics (not sure about a "shift" rather than "expansion"). Gene therapy problem is getting into all relevant cells. Ubiquitous expression of proteins the root cause of side effects for protein-based targets, possibly... - Andrew Su

(only to get the blog on top of the ISCB portal site; the figures messed up our layout) - Reinhard Schneider

Ruchira S. Datta

Birds of a Feather session: Semantic Web-Linked Data, organized by Eric Neumann, in T5

July 1 - Comment - Like - Share

Nakao M., Cass Johnston, Adam Kraut and 9 other people liked this

linked data is: a simple set of 4 guidelines for publishing RDF data on the Web (over HTTP), developed by Tim Berners-Lee in 2006 - Ruchira S. Datta

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1. Use URIs as names for things (globally unique identity). 2. Use HTTP URIs (everyone has a web browser/client) 3. When someone looks up a URI, provide useful information...in the form of RDF data. 4. Include links to other URIs (foster discovery of additional information). - Ruchira S. Datta

Context-independent identifiers (URIs) would make things so much more useful and interoperable - like Lego pieces. - Ruchira S. Datta

Some want to get the semantics exactly right and use formal logic and OWL, but here we're emphasizing just the linkability of things. - Ruchira S. Datta

A URI can only refer to one thing, but one thing can have several URIs, unfortunately. - Ruchira S. Datta

several years ago, tried to bridge use LSIDs (life science ids): thing:something:something:identifier. But this can only be recognized by some particular software, not a web browser. Strong influence from W3C to use HTTP URIs, per the law of least power: do what requires the least technology. Even Mark Wilkerson who was touting LSIDs has come around to HTTP URIs. - Ruchira S. Datta

A commenter says LSIDs still exist, it's just that they can extract them from HTTP URIs. - Ruchira S. Datta

There are other proposals, e.g., shared names; Neumann prefers even less constraint than shared names. - Ruchira S. Datta

So, now if you put in a URI you get something back. You should be able to get RDF back. UniProt does this: if you put .rdf on the end of the URI, you'll get the data back as RDF. - Ruchira S. Datta

Now colleagues can just use the URIs in order to reuse the data; don't need to copy the data. - Ruchira S. Datta

someone says the UniProt accession is an identifier, whereas the URI is a way to get at the thing through the web - Ruchira S. Datta

identifiers can overlap, but HTTP URIs put things in unique namespaces - Ruchira S. Datta

it needs to be stable: when you put this out, you're establishing a contract with the community that it's going to change - Ruchira S. Datta

currently, the url, e.g., http://www.uniprot.org/uniprot... is also the URI. the second part is the identifier of the record and the part before the slash is the namespace. At http://purl.bioontology.org, we separate the namespace and the url. So going there we have a PO box that can eternally forward it. - Ruchira S. Datta

Problem: this assumes http://purl.bioontology.org may go away. Thus the Banff Manifesto. - Ruchira S. Datta

Reduce the likelihood of catastrophic failure by consolidating it into an institution, e.g., Stanford University, with longevity. - Ruchira S. Datta

This just pushes the problem onto purl.bioontology.org. - Ruchira S. Datta

The domain name can be transferred, so why do we need purl.bioontology.org? - Ruchira S. Datta

Transferring a zillion domain names is a pain, transferring one domain name is easy. The institution commits to maintaining that domain. - Ruchira S. Datta

It should be not just the institution, but the community--the community will continue to live on. - Ruchira S. Datta

Knowledge should be monotonic: it grows and doesn't disappear. Even if a particular effort dries up, the URIs should still be valid so we can still see what was there. - Ruchira S. Datta

The Linking Open Data Project: A community project started within the W3C Semantic Web Education & Outreach group in 2007 - Ruchira S. Datta

The LOD (Linking Of Data) "cloud", May 2007: many projects with various links between them, e.g., MusicBrainz, FOAF, DBpedia, etc. - Ruchira S. Datta

By March 2008, had tripled - Ruchira S. Datta

you can put any kind of data up and make it available to Sparkle queries - Ruchira S. Datta

By September, WordNet and various other dbs had come in - Ruchira S. Datta

March 2009: life sciences comes in, with Bio2RDF - Ruchira S. Datta

now you can find the data that is in NCBI and UniProt in RDF format, but not the experimental data yet - Ruchira S. Datta

to make this useful for interesting research, will need URIs, and to figure out what are the rules that are important for life sciences - Ruchira S. Datta

when you publish using this data, how is your data that builds on top of it going to be able that's linked from it? - Ruchira S. Datta

we don't really have this concept in life sciences yet, people don't know about it - Ruchira S. Datta

suppose one looks for a concept in the LOD cloud, like "heart"; how do we know which thing to query? BioOntology, DBpedia, etc? - Ruchira S. Datta

one can't do the Google on it yet - Ruchira S. Datta

bioontology guy hates Google analogy; Google gives millions of hits, but we want the contextual query - Ruchira S. Datta

i protest, have to have indexing before ranking - Ruchira S. Datta

this doesn't solve the problem of redundancy: we want the facts about a protein, regardless of their source - Ruchira S. Datta

bioontology guy says you don't need the index to answer the query, just to answer it fast - Ruchira S. Datta

someone else says, need the indexing in order to do the clustering - Ruchira S. Datta

she says you need semantic web overlays. we need hierarchical indexing environment in order to do this at scale - Ruchira S. Datta

one needs to be able to query on an abstraction - Ruchira S. Datta

bioontology guy: what's more important, query or browsing? - Ruchira S. Datta

someone else: even browsing, if something is 3 links away, may not even go there - Ruchira S. Datta

bio2rdf guy says: first we ask everyone simultaneously: do you know about this? then we ask what do you know about it? we have implemented Shared Names. But the URI just goes to the original record. Many people have said many things about the same entity. - Ruchira S. Datta

nobody wants to have to read all the papers in MedLine. the punchline is the links: how does this protein relate to others. if we don't trust a link, *then* we want to drill down - Ruchira S. Datta

if there are 5 million sources of "A is related to B", we don't want to read all of them, we just want to know that there are 5 million of them. we also want to know the kind of evidence, e.g., particular kind of experiment. Then the user can decide whether to trust it. - Ruchira S. Datta

At this conference, enormous number of people mining data. We should be able to see their results as easily as the original sources. - Ruchira S. Datta

Great coverage! Thanx! It's like being there... would have loved to sneak in on this BoF... - Egon Willighagen

Egon: feel free to wander in... - Ruchira S. Datta

we want just the local subnetwork, not the text. we want the facts - Ruchira S. Datta

people want question answering - Ruchira S. Datta

Bing bought Powerset for this purpose - Ruchira S. Datta

someone says this turned out to be crap, e.g., "Psoriasis causes arms" - Ruchira S. Datta

the question can be a small subgraph, not necessarily an English sentence - Ruchira S. Datta

when we want information about a protein, there are only a limited number of kinds of things we can be interested in, so the software can guide the query context-sensitively - Ruchira S. Datta

we need to distinguish the problem of document retrieval from query formulation - Ruchira S. Datta

we shouldn't just think of scientists, but also other kinds of users - Ruchira S. Datta

this will all be possible, but many people are currently just reinventing RDF over and over again - Ruchira S. Datta

how many here are producers of RDF? roughly 8 - Ruchira S. Datta

put the things that we create in RDF, e.g., if you make the intersection of this fact with this paper, you are in charge of minting that URI - Ruchira S. Datta

if everyone does this, then this facilitates cross-references and exchanges - Ruchira S. Datta

http://bio2rdf.org querying life - Ruchira S. Datta

Nophar Geifman has been working with Eytan Ruppin on finding cliques in GO around different diseases. A thing like that should have an URI, so other people can use it. - Ruchira S. Datta

can we do micro-experiments so by ISMB next year, we can prove this concept - Ruchira S. Datta

paradigm shift between hypothesis-driven query versus, the data throws the hypothesis at you - Ruchira S. Datta

what's important is the use case: what is the question you can answer that would make them go "wow"? - Ruchira S. Datta

David Hune is working with FreeBase and has developed Parallax, a facet browser - Ruchira S. Datta

he also developed Exhibit - Ruchira S. Datta

faceted browsing makes more sense to biologists - Ruchira S. Datta

look at Google's Wonder Wheel - Ruchira S. Datta

Jamie Gonagell (sp??!) at SciFoo camp designs games, first slide was World of Warcraft: if you harnessed the collective brainpower that youngsters spend on WoW every day, you could rewrite Wikipedia every day! - Ruchira S. Datta

we need to figure out how to pull people in - Ruchira S. Datta

I mentioned during the session, but forgot to link here (hard to talk and type at the same time!), Marti Hearst's new book _Search User Interfaces_ http://searchuserinterfaces.com - Ruchira S. Datta

How to pull people in - that's the challenge to get this working. Could we get some seed money into this scientific effort and have it distributed with mechanisms similar to Google Adds? Yes if so we could have students and scientists putting efforts into this rather than some obscure webservers, blog etc with Google Adds. But how to generate the seed money? Government grants, donations or pay for usage? - Bo Servenius

Ruchira S. Datta

FFers open thread

June 26 - Comment - Like - Share

Pierre Lindenbaum, Cass Johnston, Nakao M. and 6 other people liked this

I'm here and will be attending the BioPathways SIG. I figured there should be some place to say non-talk-specific things like "I've arrived!", so here it is. - Ruchira S. Datta

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Will be switching between DAM, BOSC and the BioPathways. Once I've figured out which talk is when ;) - Oliver Hofmann

Uhoh. I sense a lack of places to recharge notebooks. This is going to be fun during the session breaks.. - Oliver Hofmann

I forsee a problem with the SIG posts in FF - only one heading, and many, many speakers.... Hopefully will be OK for people following. - Allyson Lister

The projectionist kindly suggested I power up in the projection cubicle during the coffee break. - Ruchira S. Datta

Network is slowing down to a crawl for me. - Oliver Hofmann

Sitting at home, following the conference. Great job folks! My only wish is that there was some place where the speakers would upload their presentations. - Lars Juhl Jensen

Help! Anyone got a UK plug adaptor with them I could borrow for an hour or so? Will happily exchange laptop charge for beer/coffee. - Cass Johnston

Oliver, I've been having that problem too. There were some times when I had posted a comment and wanted to post another one, but the first hadn't finished posting, so I had to wait for the post to finish, hold my comment in my head, and also pay attention to what the speaker was currently saying... - Ruchira S. Datta

Talked to the organizers. They are aware of the problem, IT is looking into increasing bandwidth. Yay. - Oliver Hofmann

@Oliver well done! Perhaps we could ask someone to look into more power extension leads? :) - Allyson Lister

Anyone up for a FF lunch / dinner / drink at some point during ISMB? - Oliver Hofmann

Sounds good. I'm about to go orienteering, though, so will be out of reach this evening... - Ruchira S. Datta

Monday and Tuesday are the only "free" nights, with poster sessions going from 5:45 to 8:30 pm. Shall we just set Monday night for the FF meet-up? When would people want to leave the conference at the earliest? 8 pm? - Michael Kuhn

Monday's going to be busy meeting everyone; I'd probably try and stick around 'till 8pm. Meet at the registration booth close to the entrance at 8:15? Can decide on a venue depending on our numbers and whether people are willing to travel to the city center. - Oliver Hofmann

I think I would prefer 8:40. I have a poster. I haven't figured out yet whether it's Monday or Tuesday, but others might have posters too? Last year, at least, I was explaining my poster to people pretty much constantly until the poster session closed. - Ruchira S. Datta

Monday or Tuesday is good for me - either way, and any time is fine. It's a good idea! - Allyson Lister

8:45 on Monday then, same place (registration area)? Do we have any locals with suggestions? - Oliver Hofmann

ok - see you all in registration at 8:45 monday :) - Allyson Lister

If everyone has already seen Gamla Stan by that time, we could go to Södermalm--plenty of good restaurants. I'm staying there. - Ruchira S. Datta

@Ruchira: works for me as long as we have a guide to get us there :) - Oliver Hofmann

@Allyson There are lots of power extensions along the windows just inside the T hall. Let me know if those are still too full and I'll see what I can do about getting more. - Dave Messina

@Oliver The conference organizers have bought high-speed internet. Anyone can go to the registration desk for a free login. Spread the word! - Dave Messina

@Dave, yep, got mine this morning. World of a difference. - Oliver Hofmann

@Dave, any chance of getting extension cords to the other conference rooms? Starved for outlets at K21 :) - Oliver Hofmann

I'll be arriving today, would it be worth to pack a extension cords with multiple sockets? - Roland Krause

@Roland: This is always a good idea. Problem is that some rooms only have power on the stage and in the projection booth. - Michael Kuhn

Organizers also have extra extension cords for emergencies, but even the main conference room has no outlets. Best to recharge during the breaks, but that means leaving the notebook unattended... - Oliver Hofmann

photos from ISMB/ECCB, please put on flickr under tag "ismbeccb2009" - Burkhard Rost

The projectionist here just unplugged my power cord from their outlet and said none of us will be allowed to use their outlet; we'll need to use the outlets in Hall C. He said the organizers did not pay for extra outlets, so we will still have this power problem. - Ruchira S. Datta

Well, at least I'll be able to sit closer to the front where I can see better. - Ruchira S. Datta

Even the "free" network is considerably faster and more responsive today. Well… we'll see what happens when the first coffee break hits. - Johann Visagie

@Ruchira: Ouch. That's not going to help. We can get extension cords and use them in the smaller meeting rooms though. - Oliver Hofmann

@Johann agreed - I also think the network is faster today - Allyson Lister

I love the fierce, ofttimes violent competition for the limited resource that is power outlets during coffee break! - Johann Visagie

It seems a simple #ismb is the twitter hashtag of choice. Also note Burkhard's suggestion above to use "ismbeccb2009" as Flickr tag. (Hey! Flickr tags can has spaces! ;) - Johann Visagie

@Johann: Bring your own socket multiplier and you are loved by everyone ;-) - Oliver Hofmann

Any chance of leaving / recharging our desktops at the registration desk during the breaks? Would rather not leave mine in a conference room unattended. - Oliver Hofmann

Lonely FFer near the registration desk is looking for some chatting... anyone? - Egon Willighagen

Sure, I'll wander by momentarily. - Ruchira S. Datta

I'm sitting on the ground in front of the registration desk, waering a black t-shirt... - Egon Willighagen

Any poster presenters here on FriendFeed? Maybe you can start a new post in the ISMB/ECCB room and attach your poster PDF? - Egon Willighagen

Great idea, Egon! Not being at the conference, I would very much appreciate being able to see some of the posters on FF. - Lars Juhl Jensen

Lars, are you in Stockholm? - Egon Willighagen

What about special sessions, I do not see them here. - Diego M. Riaño-Pachón

I'm having a special FF sessions outside, but I am the only participant :) (after a nice meet up with Ruchira earlier) - Egon Willighagen

@Egon - shame - I was offline for lunch. At least I assume it was lunch you said that. FF doesn't put up the time each comment was made - so add times please if you're talking about meetups! Hopefully see most of you this evening after the poster session anyway :) - Allyson Lister

P.S. The network seems to have slowed down again. Anyone else notice, or is it just me? - Allyson Lister

@Dave thanks for the power extension cable - except for the main victoria hall (as we discussed) it's really helped a lot :) - Allyson Lister

@Allysin, I'm still around... in front of E.A.T. now.... - Egon Willighagen

@Egon - ah, but I'm in a talk! :) - Allyson Lister

@Egon, no I decided not to go this year - Lars Juhl Jensen

@Allyson: As half of the conference is probably sharing the username / password for the closed network I am not surprised it is slowing down :) - Oliver Hofmann

Maybe it is because I am happily uploading Jmol 11.7.45 to SourceForge ? :) - Egon Willighagen

@Allyson Glad to help! - Dave Messina

@Oliver Hopefully it's that rather than someone downloading Genbank. :) Still plenty of FREE logins for the closed wifi are available at the registration desk for anyone who wants one. - Dave Messina

Fun to see how quickly many of us have found a workaround for the 'Oops'... :) - Egon Willighagen

Is there a place for posting jobs/student positions available to ISMB attendees? (i.e. http://tinyurl.com/brinkma...) I'm not at the ISMB this year, so am definitely checking out FF and related resources and thank you all for your posts! - Fiona Brinkman

Does anyone know how to 'filter out' all group:ismbeccb2009 messages in my main feed? So that I can just open the ISMB/ECCB 2009 group in a separate window? - Egon Willighagen

Thanks to everyone - organizers, reviewers, presenters, friends, bloggers etc etc etc : I must away, but had loads of fun! :) - Allyson Lister

@Allyson, safe travels. @all, see you in Boston. Feel free to PM/mail me for tips where to stay, eat or party in the city. - Oliver Hofmann

nice meeting you, Allyson, and have a safe trip! - Ruchira S. Datta

I am leaving too, was nice meeting you all and have a good trip back. - Roland Krause

Conference finally closed. - Peter Menzel

i'm now at the Stockholm airport en route to Cambridge for another conference (!) http://www.functionalgenomics.org.uk/section... It was fun meeting some of you and microblogging together. Hope we'll see each other around at future conferences. Next year in Boston! - Ruchira S. Datta

@Egon: if you go to the ismbeccb09 room and click the "(edit)" link to the right of "Lists" then you can deselect it from your Home feed. - Lars Juhl Jensen

A top-ten of talks (well, not really - just the top ten of my ISMB posts based on number of hits). What was everyone interested in enough to click through to my blog? Find out: http://themindwobbles.wordpress.com/2009... - Allyson Lister

Lars Juhl Jensen

Wordle cloud of the contributors (as requested by Cameron Neylon)

July 2 - Comment - Like - Share

Nakao M. and Pierre Lindenbaum liked this

mm strange the first and second names dont seem to correlate can you combine them? e.g "allyson lister" - Frank

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no, sorry - I have not found a way to make Wordle keep words together - Lars Juhl Jensen

with an underscore ? - Pierre Lindenbaum

underscore does not seem to work either - CamelHump? AllysonLister? - Frank

yes, Frank - that will obviously work (see new post) - Lars Juhl Jensen

Oliver Hofmann

ISMB/ECCB Stockholm 2009: Bioinformatics Core Facilities Workshop, Fran Lewitter

July 2 - Comment - Like - Share

Neil Saunders liked this

Project priorities: just long term misses new customers, grant opportunities. Focus on money or project size misses pilot projects, does not allow diversification. Suggestion: based on merit, what allows the core to grow in new directions, expand, supports the institutional community in general - Oliver Hofmann

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Hiring: 50% FTE available for a new person, enough to get someone started. Identify new technologies, hire to get an early start. Consultants can fill gaps. - Oliver Hofmann

Time: maintain an overview of timeframes (putative project starts). Wrap up projects to avoid task switching overhead as much as possible. Make time for the planning stages. - Oliver Hofmann

Expectations: be open and transparent with regards to availability, feasibility, stick to realistic time estimates and turn down work if the resources are not available. Collaborate between Cores - Oliver Hofmann

Cancer UK, Cambridge Core. Prioritize short tasks, genomic tasks. Use queuing system, use steering committee to guide on participation in long term researcher-based projects - Oliver Hofmann

usually 6-10 projects per person at any given time (ouch...) - Oliver Hofmann

Manage workload: define scope early, manage using collaboration software, deliver data in stages - Oliver Hofmann

automate and standardize - Oliver Hofmann

Training / empowering researchers the most important aspect - Oliver Hofmann

Report regularly to all groups / departments, communicate - Oliver Hofmann

Request co-authorship (but do not seem to require it) - Oliver Hofmann

Start of discussion - Oliver Hofmann

Current developments and changes: focus on next-gen - Oliver Hofmann

Benefits of training - Oliver Hofmann

Chargeback model. half of participants fully supported by their institutes - Oliver Hofmann

Hourly charges between 70 and 120$ - Oliver Hofmann

Authorship: mostly just acknowledgement, many cores with focus on master's level students - Oliver Hofmann

Collaboration: central place to share knowledge of methods, tools, evaluation. One place to deposit this information could be the http://www.bioinfo-core.org/index... - Oliver Hofmann

Try to find ways to pool information and resources (similar to the BOSC OpenBio projects) - Oliver Hofmann

Switch of topics on how to handle next-gen seq influx - Oliver Hofmann

What kind of questions are being asked, can they handle the data themselves, and is there any way to build re-useable workflows? Experience seems to be that so far no question (beyond the assembly step) has come up twice. - Oliver Hofmann

Develop method agnostic tools that help the biologist to get a handle on their own data, Eg http://www.bioinformatics.bbsrc.ac.uk/project... - Oliver Hofmann

Lots more notes over at http://www.fiamh.info/article... - Oliver Hofmann

Mikhail Spivakov

Special Session 6: Regulatory Genome Architecture and Noncoding Mutations in Human Disease

July 2 - Comment - Like - Share

Carl Fulp liked this

Talk: Veronica van Heyningen, "Lessons from regulatory mutations in developmental anomalies" - Mikhail Spivakov

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Highly conserved non-coding DNA seqs emerge as regulator elements - bind multiple TFs - Mikhail Spivakov

Genes with complex expression patterns require complex control - Mikhail Spivakov

Disease-associated chromosomal breaks outside gene highlight distant regulatory elements, often within neighboring genes - Mikhail Spivakov

Different mechanisms of disruption: - Mikhail Spivakov

key elements separated from transcriptional unit - total loss of function - Mikhail Spivakov

altered chromatin organisation (originally position effect variegation) - Mikhail Spivakov

ah, lecturer from my undergrad days. - Neil Saunders

Pax6, Spx2, Otx2 - genes with important role in eye development that are also important in the brain; continue to be expresed in the adult organism as well - Mikhail Spivakov

Explore Pax6 long-range control elements - up to 180 kb away from the gene - Mikhail Spivakov

use distant elements in reporter transgenic analysis to look at expression patterns they drive - different elements drive expression in different tissues at different times. however, find large overlap, so there's no easy rule according to which distant regulatory elements work together to establish the expression pattern - Mikhail Spivakov

some distant elements are within a neighboring housekeeping gene - Mikhail Spivakov

study deletions in various regions by using a reporter construct, compare with isolated enhancer function - Mikhail Spivakov

find an element in Pax6 intron that drives expression in the (zebrafish) heart - unexpectedly - Mikhail Spivakov

also find a Pax6-response element: autoregulation - Manuel et al, Development, 2007 - Mikhail Spivakov

a mutation in a Pax6 reg element located in the intron of the neighboring gene has been associated with (a mild form of) epilepsy - Mikhail Spivakov

some enhancers work only at later developmental stages (eg, E17.5) - Mikhail Spivakov

need methods for phenotype prediction based on regulatory mutations - eg, enhancer-driven knockouts - Mikhail Spivakov

in zerbafish, there are pax6 forms - pax6 a (expressed in the barin), pax6b (expressed in the pancreas), both are expressed in the eye - Mikhail Spivakov

the regulatory elements for the brain were lost from pax6b, pax6a has lost its neighboring gene (ie, the reg elements located within it), pax6b retained some a part of it - Mikhail Spivakov

Move to Sox9 - Mikhail Spivakov

haploinsufficiency causes campomelic dysplasia and sex reversal - the breakpoints can be very far away, the severity of phenotype decreases with the breakpoint position being further away - however mutations causing Pierre Robin syndrome may localise to a very specific long distance element ~1.1 Mb away from the gene, small deletions at 1.4 Mb upstream _AND_ 1.4 Mb downstream. How these elements work together is yet to be determined. - Mikhail Spivakov

Another example: Van der Woude severe phenotype caused by intragenic mutations in IRF6; a regulatory variant of IRF6 (a SNP upstream of the gene, disrupting an AP2alpha binding site) predisposes to sporadic CLP (cleft lip and palate) - Mikhail Spivakov

Discuss developmental abnormalities caused by mutations in SHH (sonic hedgehog) - Mikhail Spivakov

a related phenotype is produced by an insertion in the intron of a neighboring gene - LMBR1 - Mikhail Spivakov

Pax6 and Sox2 interact to cross and autoregulate, mutations in the "double" binding sites (ie for both) at different cells result in mutant phenotypes. Note that TF dosage is important. - Mikhail Spivakov

Next talk: James P. Noonan, The Role of Developmental cis-Regulatory Change in Human Evolution - Mikhail Spivakov

what makes us human? unique abilities <- developmental changes (brain, limbs etc). What's the molecular basis of these traits? - Mikhail Spivakov

changes in gene regulation vs changes in genes themselves. perhaps there's a lot of the former (in the evolution of primates) - Mikhail Spivakov

two approaches: 1) in vivo chacaterization of cis-regulatory modules with human-specific developmental functions, 2) whole-transcriptome comparative analysis - Mikhail Spivakov

start with (1). how to identify developmentally active CRMs in the human genome? - Mikhail Spivakov

the more conserved an element is the more likely it'll function as an enhancer - Mikhail Spivakov

also look at chromatin signatures - for example, p300 binding sites are 90% predictive of enhancers (Visel et al, Nature 2009) - Mikhail Spivakov

look for noncoding elements that are conserved across species but rapidly evolve in humans - human-accelerated conserved noncoding sequences (HACNSs), Prabhakar et al, Science 2006. - Mikhail Spivakov

Developed stats models to measure evolutionary rates, estimate probability of human-specific substitution, calculate likelihood of observed pattern of substitutions in each noncoding element - estimate acceleration p-value. Identified 992 HACNSs out of ~10000 conserved elements - Mikhail Spivakov

associate with neighboring genes -> GO analysis. only 1/734 functional categories showed significant association: cell adhesion! More detailed look - neuronal cell adhesion, axon guidance, synapse formation - Mikhail Spivakov

Do HACNSs function as reg elements in vivo? Transgenic assays in mouse (select elements based on overall constraint and human-specific acceleration). Many elements show specific developmental patterns of expression in these assays - Mikhail Spivakov

Focus on HACNS1 - associated with gbx2, highly conserved in all terrestrial vertebrates, evolving 4x faster than neutral rate in human, sequence changes are fixed. The sequence change is association with a gain of function: human-specific anterior limb expression. - Mikhail Spivakov

this gain of function has been achieved by 13 substitutions in the sequence compared to chimp (proved by "humanizing" the chimp region and "chimping" the human region by making these substitutions) - Mikhail Spivakov

drives expression in the anterior-most digit at e13.5 - may contribute to the development of longer thumbs in the human compared to chimp/orangutan? - Mikhail Spivakov

HACNSs: selection or biased gene conversion? Biased gene conversion - postulated to increase the fixation rate of AT to GC substitutions. Mutagenic effect of recombination hotspots + preference in recombination-associated DNA repair toward GC vs AT pairs. - Mikhail Spivakov

Synergy between positive selection and BGC in HACNS1? - Mikhail Spivakov

HACNSs are not biased towards high-recombining regions. The human-specific substitution rate is not elevated outside of HANS1 - but GC rate is. - Mikhail Spivakov

Move from genotype to phenotype: comparative gene expression profiling in developing cortex. - Mikhail Spivakov

Mouse vs human fetal forebrain, look at gene expression profiles of several cortical stem cells by RNAseq. Purify cell populations by laser capture microdissection. (collaboration with Rakic/Ayoub @ Yale). Recover 50 ng of total RNA from ~10,000 cells, which is more than enough for RNAseq. Comparison of different cell populations in the developing mouse cortex - very high correlation of expression. Differentially expressed genes "make sense". - Mikhail Spivakov

Ultimately, want to associate differentially expressed genes with HACNSs - Mikhail Spivakov

Next talk: Steve Montgomery, Population genomics of human gene expression using next-generation sequencing technology - Mikhail Spivakov

looked at two different quantitative traits: exon reads and splicing pairs - Mikhail Spivakov

~80% reads map to known exons. 40% reads span multiple exons (insert size: ~150bps) - Mikhail Spivakov

data normalisation of RNAseq data is still a challenge. used a simple scaling approach - Mikhail Spivakov

test data filter criterion: <10% of individuals equal to zero - Mikhail Spivakov

see ~ 11,000 genes, corresponding to ~95,000 exons; ~23,000 exon pairs -> from 1 lane per individual. - Mikhail Spivakov

there's a decent correlation between any two individuals (same sample same run: corr=0.93, diff sample, same run: corr=0.89, diff sample, diff run: corr=0.86) - Mikhail Spivakov

Correlation of exon reads within genes (test for freq of alternative splicing) - corr is good, but not perfect for exons with high mean read count, so some information is escaped by array analyses that assume a fixed exon structure for each gene. - Mikhail Spivakov

Adding a number of lanes / individuals increase the number of identified splice variants => many of alternatively spliced transcripts are rare - Mikhail Spivakov

Detecting eQTLs with RNAseq data: assume an additive model of gene expression, for each SNP look at the number of reads, use spearman rank correlation to assess the association - Mikhail Spivakov

detected 2431 genes (4219) exons associated with SNPs at p~0.01 - Mikhail Spivakov

eQTLs detected with exon counts centred around TSSs - Mikhail Spivakov

consider using RNAseq to detect SNP association with known splice variants - took 1767 known splice variants from Ensembl, tested for association against splicing pair counts, data look promising - Mikhail Spivakov

Q: what cells used? A: EBV-transformed lymphoblastoid cells. Q: is this a bit of a constraint to look only at these cells? A: looked at eQTLs in other lymphoblastoid cell lines collected long time ago, see a lot of correlation. Did not look at other tissues. - Mikhail Spivakov

Q: did they look at 20% unannotated exons? A: No, can't do much until new gene models are built from them. - Mikhail Spivakov

Q: where are the SNPs? Association with HCEs? Gene functional categories enriched for SNPs? - Mikhail Spivakov

A: in 1Mb windows, see enrichment for eQTLs right around the TSSs rather than remote regulatory regions. Not a large number fall within known regulatory elements. - Mikhail Spivakov

Next talk: Nadav Ahituv, Deconstructing gene regulatory elements - Mikhail Spivakov

Geneticists are good at finding genes from sequence, can do much less with detecting regulatory elements - in the vast space of 98% of the genome that is non-coding. Also don't know the effect of nucleotide substitutions at regulatory elements. - Mikhail Spivakov

What can we do about it? 1) use comparative genomics to find conserved non-coding regions. 2) high-throughput characterisation of enhancers - Mikhail Spivakov

At Berkley, looked at extremely conserved non-coding sequences (n~3000, 70% similarity, >=100bp human-fugu) and ultracobserved (n~250, 100% similarity). Many of them turn out to drive expression in transgenic assays in the mouse. Now moved to UCSF, are setting up the same assays in zebrafish - easier to move it to high-throughput analysis - Mikhail Spivakov

enhancer.lbl.gov: resource for experimentally validated human noncoding fragments with gene enhancer activity as assessed in transgenic mice. - Mikhail Spivakov

These data can be used in a variety of ways. They aim to understand the regulatory code at enhancers. Look for limb-specific signatures, check whether they see them at limb-associated genes, check for new regions with these signatures in the human genome, test in zebrafish (expression in fin), if positive check in mouse (expression in limb) - Mikhail Spivakov

look at ~480 ultraconserved elements (>50% non-coding, 100% identity and <=200b human-mouse-rat), depleted for SNPs - Mikhail Spivakov

extreme sequence constraint = extreme functional constraint? - Mikhail Spivakov

took four UCE: positive in enhancer assays, near genes when mutated lead to either a lethal or sexual development phenotype, variable in size - Mikhail Spivakov

generated mouse knockouts for these UCSs - heterozygous KOs are fine, even homozygotes have no apparent phenotype!!! - Mikhail Spivakov

so why is it? - Mikhail Spivakov

maybe we just can't detect the phenotype? - Mikhail Spivakov

maybe there's gene / reg module redundancy? It certainly exists - eg at UCEs upstream of ARX - Mikhail Spivakov

maybe it's because mutations will cause gain-of-function (by binding of other TFs) rather than loss-of-function? in this case, deleting the whole thing altogether won't help identify this - Mikhail Spivakov

support for this model: replaced a limb enhancer in mouse with a bat enhancer that has only 20bp difference -> observed limb elongation. Also bioinfomatic support showing that these seq's are prone to substitutions and indels (?) - Mikhail Spivakov

Take four UCE that they KO'd, put an 83bp indel and introduced a 3bp change, both chosen more or less randomly. Very preliminary results on the 83bp insertion into two of the enhancers: made mice, after 10 generations of backcross, het:het mating recovers fewer heterozygous and homozygous mice than expected. - Mikhail Spivakov

Neil Saunders

Come on, get those photos up! Just kidding, you've all been busy (and done a great job) blogging.

July 2 - Comment - Like - Share

Allyson Lister liked this

I brought my camera on Monday, but did not make any pictures... no excuse! - Egon Willighagen

ISMB/ECCB

TT48: David Croft - Reactome tools for expression data and pathway visualization

July 1 - Comment - Like - Share

Reactome collects processes at the cellular level. - Gabriele Sales

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Website: http://www.reactome.org - Gabriele Sales

Plans for a new visualization for the website. - Gabriele Sales

At the top of the reactome webpage there is a link pointing to the new interface. - Gabriele Sales

The left bar of the interface collect links to single pathways. - Gabriele Sales

Google Map-like buttons: zoom in / out, scroll. - Gabriele Sales

By clicking on a compound, list of other pathways it participates to. - Gabriele Sales

Free text searches: multiple results displayed in a tab. - Gabriele Sales

IntAct web tool: http://www.ebi.ac.uk/intact/ - Gabriele Sales

The ENFIN project: http://www.enfin.org/ - Gabriele Sales

ISMB/ECCB

TT47: Chris Rawlings - Semantic Data Integration for Systems Biology Research

July 1 - Comment - Like - Share

Keywan, Simon Cockell, Jim Procter and Cass Johnston liked this

Also speaking: Catherine Canevet and Paul Fisher - Allyson Lister

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Two systems to integrate data. - Gabriele Sales

BBSRC-funded research collaboration in Newcastle, Manchester, and Rothamsted : ONDEX and Taverna - Allyson Lister

Demo on the integration and validation of yeast metabolome models. - Gabriele Sales

ONDEX: http://www.ondex.org/, taverna: http://taverna.sourceforge.net/ - Andrew Su

Taverna is a workflow workbench to integrate tools (including web services). - Gabriele Sales

Taverna can link ONDEX and external (ex. PubMed) data sources via the web-service interface. - Gabriele Sales

When ONDEX works with Taverna, instead of using the pipeline manager you use the ONDEX web services and access ONDEX from Taverna. This means you can use Taverna to pull in data into ONDEX. - Allyson Lister

Outline of the demo: starting from Janboree Network SMBL, parse it into Ondex, remove currency metabolites and annotate using network analusis results. - Gabriele Sales

Then switch to Taverna. Identify orphans, retrive related enzymes, assemble a PubMed query and link results to the graph. - Gabriele Sales

the workflow for relevant pubmed entry retrieval seems staggeringly complex - but I guess this is because each input appears as a node in the workflow (is that correct ?) - Jim Procter

# ondex vs cytoscape? - Andrew Su

@Andrew - not sure - ondex uses Jung as the underlying layout engine (and Alan Kuchinsky of Cytoscape is asking a question!) - Jim Procter

Question: how does the system scales for large amount of data? - Gabriele Sales

@Jim, but they are similar use cases covered btw the two systems? - Andrew Su

Blog post: http://themindwobbles.wordpress.com/2009... - Allyson Lister

@I think there are but the response to that question seemed to suggest that ondex was aimed at denovo network generation rather than massive visualization (this needs to be clarified) - Jim Procter

@Jim, thanks... - Andrew Su

ISMB/ECCB

HL54: Mona Singh - Search and discovery of recurring patterns with interactomes

July 1 - Comment - Like - Share

Neil Saunders liked this

Hairballs. - Roland Krause

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Different large scale data sets, genetic, phosphorylation etc. exist but how to interpret? - Roland Krause

Add protein annotatons, sequence, structure, motifs, domains, functional characterization. - Roland Krause

Particular interested in interaction domains, analyzing cellular organization and interactomes. Can we discover and analyze recurring patterns. - Roland Krause

Analogy to multiple alignment of protein sequences with PROSITE pattern - Roland Krause

For networks schemas, nodes are description of proteins, e.g. domains. An extension of network by attributes, e.g. PFAM or PROSITE. - Roland Krause

Examples for network schema are homologous pathways. - Roland Krause

Netgrep has visual interface. - Roland Krause

No details of the algorithm, tricky problem but can solve it fast. - Roland Krause

Triangles, quad topology (linear combination of four), Y star topology of four. - Roland Krause

Automatically discovery of overrepresented schemas with direct interactions and sequence motifs. Using Y2H with filtering to address quality of the data set. - Roland Krause

Counting occurrences of labelled subgraphs, brute force approach using Netgrep. - Roland Krause

score each possible schema - Ruchira S. Datta

count how frequently it occurs, but different annotations have different frequencies - Ruchira S. Datta

need to account for overrepresentation - Ruchira S. Datta

Some annotations are more frequent than other, score has to incorporate both the frequency. - Roland Krause

Randomized network - Roland Krause

take each network, randomize it, count how often the annotation occurs in the randomized network and compute the overrepresentation term - Ruchira S. Datta

Estimate false discovery rate, look at features with FDR < 0.05 - Roland Krause

count how often the score occurs in the random graph, to estimate the false discovery rate - Ruchira S. Datta

when making the random graph with the pair schemas, preserve degree - Ruchira S. Datta

for triplet schemas, also preserve annotation - Ruchira S. Datta

For 3-vertex schemas, need to presever pairwise annotation acounts. - Roland Krause

for higher order schemas, also preserve triplets - Ruchira S. Datta

used Stub Wiring from Uri Alon's group for randomizing the pairwise schema - Ruchira S. Datta

no known algorithm for randomizing uniformly, need to approximate - Ruchira S. Datta

151 pairwise schema [...] - Roland Krause

do the proteins making up these schemas share biological processes? - Ruchira S. Datta

Hypergeometric evaluation of schemas. - Roland Krause

check enrichment versus background - Ruchira S. Datta

Graph of the pairwise schema network. - Roland Krause

For triplets, nodes are themselves pairwise schemas. - Roland Krause

Hubs in the graph are ras, kinas and [...] - Roland Krause

cross-interactomics: repeated the process in human - Ruchira S. Datta

Example of the DUP family in yeast, and pair comparison between human and yeast. - Roland Krause

Human-specific schemas, some consist of domains that also exist in yeast. - Roland Krause

Q. Robustness of the resulting networks. A. Removed 5%, found the network to be stable. Different results in different organisms. - Roland Krause

Q. Use of subgraph sampling? A. Can use any topology for searches. - Roland Krause

# Not sure I understand the question and answer but they do. - Roland Krause

Q. (Ruchira) Human-yeast network did you check orthology? A. Used PFAM annotation, did not worry about orthology. Some motifs in human are from the expansion. - Roland Krause

ISMB/ECCB

HL55: Michael Sammeth - The Computational Exploration of (Alternative) Splicing Mechanisms

July 1 - Comment - Like - Share

Nakao M. liked this

Numbering all possible splice variant sites, assign ASCII symbol to each site, "alternative splicing code" that captures all differences between alternative splicing variation - sebi

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ASTALAVISTA web service generates these strings at http://genome.imim.es/astalav... - sebi

ESTs can be truncated, and still splicing events can be detected as a sub-structure - sebi

"Bubbles" are cyclic graphs, complete events of splicing. Can construct bubble hierarchies for very complex splicing loci. - sebi

Workflow: Gene annotation -> database of events -> visualization with ASTALAVISTA; optionally add RNA-Seq data for expression levels of events (even simulated data from the Flux Capacitator) - sebi

ISMB/ECCB

HL56: Kevin Cohen - Nominalization and alternations in the language of molecular biology: Implications for text mining

July 1 - Comment - Like - Share

nominalizations are dominant in biomedical texts, e.g. "expression" is much more used than "express" - Michael Kuhn

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Cohen et al, 2008 [not a very useful reference]: nominalizations are more difficult to handle than verbs, but can yield higher precision - Michael Kuhn

http://www.plosone.org/article... - Michael Kuhn

alternation: variations like active/passive. much less characterized for nouns than for verbs - Michael Kuhn

e.g. pre-nominal arguments: agent: "phenobarbital treatment" or patient: "cancer treatment" - Michael Kuhn

previous work has tried to handle nominalizations, e.g. Ono et al (2001): interactions, association, complex and binding - Michael Kuhn

genescene: http://doi.ieeecomputersociety.org/10... [?} - Michael Kuhn

use in-house tool to do annotation of nominalizations - Michael Kuhn

alternations are very diverse, contrary to previous prediction that there would only be a limited number of alternations in scientific literature (sub-language model) - Michael Kuhn

ISMB/ECCB

HL53: Chris Taylor - Promoting coherent minimum reporting guidelines for biological and biomedical investigations: the MIBBI project

July 1 - Comment - Like - Share

Cass Johnston liked this

Standards are hugely dependent on their respective communities - Allyson Lister

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Much of biological experiments can fall under an ISA (Investigation-Study-Assay) structure. - Allyson Lister

You should then use three types of standards: syntax (FuGE, ISA-TAB etc), semantics, and scope. MIBBI is all about scope. - Allyson Lister

Why do we care about standards? Data exchange, comprehensibility, and scope for reuse. - Allyson Lister

"Metaprojects": FuGE, OBI, ISA-TAB - draw together many different domains and present in structure/semantics useful across all. - Allyson Lister

When the independent MI projects overlap, arbitrary decisions on wording and substructuring make integration difficult. This makes it hard to take parts of different guidelines - not very modular. This is what MIBBI helps with. - Allyson Lister

MIBBI promotes gradual integration of checklists. - Allyson Lister

Nature Biotechnology 26, 889 - 896 (2008) doi:10.1038/nbt0808-889 - Allyson Lister

Blog post: http://themindwobbles.wordpress.com/2009... - Allyson Lister

ISMB/ECCB

HL52: Georg Zeller - Characterizing transcriptome plasticity using whole-genome tiling arrays and machine learning

July 1 - Comment - Like - Share

Neil Saunders liked this

Motivation: find all genes in the model plant Arabidopsis thaliana. - Gabriele Sales

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profile transcriptome changes under stress - Michael Kuhn

tiling arrays: cost-effective, but noisy - Michael Kuhn

normalization pipeline: background correction to reduce imaging artifacts - Michael Kuhn

quantile normalization: comparison between arrays - Michael Kuhn

Normalization: background correction, quantile normalization between arrays, transcript normalization (to remove probe sequence bias) - Gabriele Sales

transcript normalization: probe sequence bias reduced - Michael Kuhn

Not all exon probes show the same level. - Gabriele Sales

assume that ideal transcripts have constant level of expression, try to predict deviation between actual and ideal signal intensities - Michael Kuhn

Sequence-based quantile normalization: exon and intron sequences are normalized to 2 distinct levels - sebi

Website: http://www.fml.mpg.de/raetsch... - Gabriele Sales

transcript normalization improves normalization between background and exon signals - Michael Kuhn

developed own segmentation algorithm, http://www.fml.tuebingen.mpg.de/raetsch... - Michael Kuhn

Goal: characterize tiling arrays probes into exonic, intronic and intergenic. - Gabriele Sales

mSTAD: a hidden Markov-SVM - sebi

mSTAD approach: Zeller et al., Pac Symp Biocomp 2008 - Michael Kuhn

mSTAD approach: a state is associated to each probe given its level and its context. - Gabriele Sales

mSTAD vs Affymetrix TAS - Gabriele Sales

URL: http://www.weigelworld.org/resourc... - Gabriele Sales

can also find new transcripts that are not covered by ESTs/cDNAs so far - Michael Kuhn

can validate 37 out of 47 tested cases - Michael Kuhn

Examples of differential expression: stresses induce the transcriptions of extra regions. - Gabriele Sales

mSTAD can identify previously unannotated exons - sebi

find new stress-induced TARs - Michael Kuhn

could be: stress-induced alternative transcripts, overlapping transcripts, or new stress-induced genes - Michael Kuhn

Validation via RT-PCR. - Gabriele Sales

Zeller et al, Plant J, 2009 - Michael Kuhn

predict new genes if distance >500 nt to the nearest annotated gene - Michael Kuhn

last part of the talk: analysis of dicer mutant (DCL1). DCL1 is unvolved in processing miRNA precursor genes into functional miRNA - Michael Kuhn

in dcl1 knock-out mutatants, substrate transcripts of DCL1 accumulate - Michael Kuhn

findings: many intergenic TARs are targets of DCL1 - Michael Kuhn

dcl1 is also involved in the silencing of transposons. - Gabriele Sales

DCL1 is involved in transposon silencing: find strong expression of transposons in dcl1 mutant - Michael Kuhn

outlook: include sequence effects (e.g. GC bias, seen in RNA seq) into transcript normalization - Michael Kuhn