What I think is interesting is still finding a lot of people that work in cell signalling and still don't think too much in terms of protein disorder. That disorder is viewed a lot as those parts connecting the functional domains as opposed to those parts where a lot of the function resides (post translation modifications/combinations). In a meeting Toby Gibson (from EMBL) was arguing...
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- Pedro Beltrao
I was actually at a talk by Keith Dunker, and someone from the audience started to argue with him if disordered proteins actually exist or are they merely "switching" between several stable conformations... I was amazed that there are still non-believers. Do you know anyone who doesn't believe in intrinsically disordered proteins ?
- Nir London
In the department retreat last year one of young PIs was more or less also dismissing disorder in his talk but I did not have a chance to talk to him afterwards so I am not sure what he thinks about it. Maybe it is not very intuitive to imagine the function of disordered parts if you don't work with protein interactions mediated by linear motifs.
- Pedro Beltrao
Maybe people should use an oxymoron "non-standard secondary structure" instead of "intrinsic disorder"? There would be way less opposition to such description ;)
- Pawel Szczesny
you are probably right Pawel but that is way too long ;)
- Pedro Beltrao
"alternatively ordered", "differently ordered", "specially ordered", "order-challenged", "entropically enhanced"... the possibilities are endless!
- Iddo Friedberg
Ask TLS: using HMMER for short DNA sequences (transcription factor binding sites). I am building the HMMs from MSAs of known TFBS sequences. However, using the HMM for searches on the test set (form which the TSBS sequences were initially derived) yields poor results, scorewise and evaluewise. Help? Happy New Year!
Are you using HMMER 1.8.2? I thought HMMER2 didn't model DNA sequences properly according to Sean. You may also have to explicitly revcomp the query db as well.
- Jason Stajich
Ha! Thanks Jason & Neil. Yes, HMMER2 is not suitable, reverted to HMMER1.8.5 which seems to provide much better results on the train/test set. The trouble with most TFBS web resources, is that they lock you into using TFBS and/or organisms that I don't have/need. The closest I have is PRODORIC (whose MSAs I am using to generate my HMMs) http://prodoric.tu-bs.de/ for bacteria, but...
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- Iddo Friedberg
@Neil. MAST/MEME didn't work out well. I'll try GLAM2, not sure how well this will work, the motifs are very short (15-25) and ungapped.
- Iddo Friedberg
Short/ungapped should be no problem. There's another good online motif tool that I've used in the past and can't recall the name/URL just now...I'll post here when it comes to me.
- Neil Saunders
In my hands H2 outperformed H1 on ncRNA datasets: http://genome.cshlp.org/content... However these where longer motifs than what you're likely to be using. Also, you need to include the reverse-compliment in your search DB since H2 wont do this for you. H3 looks promising for nucleotides also, however the filters expect short(ish) sequences in your search DB -- hence chromosome 1 and friends will need frag'ging.
- Paul Gardner
By conventional photolitography, Sokolov and colleagues from Argonne National Laboratory, report on PNAS the design of microscopic gears (6 ug mass) able to extract useful work from swimming Bacillus subtilis. According to their calculations, few hundred bacteria work together in order to turn the gear at a velocity of 1-2 rpm, generating femtowatt power.
- Iddo Friedberg
from Bookmarklet
Comment posted on Blog: You say, "Here the concept is that brownian motion can generate directed motion..." I'd say it's not Brownian motion that is creating the directed motion...The bacteria actually have flagellar motors that propel the bacteria. So the bacteria provide the energy (via ATP). Non-swimming bacteria (which would undergo Brownian motion) would not propel the gears, as I...
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- Steve Koch
96well's response: "Yes, thanks. Bacteria are swimming (and not floating) because of flagella, and yes: ATP and not real Brownian motion is responsible to the movements. I feel sometimes 'brownian motion' is used (non very properly) to describe bacterial motility just because the linear trajectory operated by the flagellar motor turns rapidly into new directions with a pattern which...
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- Steve Koch
The Brownian thing made me think: is there any demonstration of behavioral swarming in microbes, the kind we get in locusts, bees & college students?
- Iddo Friedberg
Ask TLS: is non-access to published literature a problem for those who have reviewed manuscripts? It never occurred to me until I had to review something, wanted to check a few references, and found them behind a pay-wall...
Is there a precedent for the journal reviewing a manuscript paying for reviewers to access subscription-only articles at other journals, or, heaven forbid, for reviewers to pay for access themselves? Or is it that reviewers check references so rarely that it just isn't an issue? When they do happen to come across one they don't have access to, do they just go "meh" and move on?
- Shirley Wu
Also, I suspect that since many reviewers are well-ensconced in the cozy surroundings of their institutional subscriptions, this occurs much much much less often for them than it would for a reviewer like me, who is not in academia...
- Shirley Wu
Despite my academia-level access, I frequently find myself unable to read references I want while reviewing. If they are essential to my understanding or my argument, I post to the RW room; if that fails I note in my review that I think [cite] is important but I was unable to access it. I suspect that most reviewers go with "meh" though...
- Bill Hooker
Thanks, Bill, those are good alternatives to going "meh" ;).
- Shirley Wu
from twhirl
JMB give 30 day access to a large range of literature to their referees via a temporary account on Scopus.
- Iddo Friedberg
from Android
Kudos to JMB -- I'm surprised, because that is tacit acknowledgement that there's an access problem, which is something that most publishers deny.
- Bill Hooker
Reviewing for cross disciplinary journals can require access to many different journals. As Bill H notes, academia access is no guarantee of access.
- Bill Anderson
from twhirl
Though it involves paying $$ -- Deep Dyve is what I've been recommending to health providers not associated with academic institutions. At $19.99/mo for unlimited access, it's not a bad price, though the site's received some negative reviews for its search engine. I haven't given it a try, though, so don't know how specific one needs to be to get to a precise article. This testing is on the list for the new year!
- Mickey Schafer
Just for fun, I ran "autism prosody" at Deep Dyve, and although the citation count was absurdly high, the first dozen or so articles are the same ones that come up in gopubmed or novoseek. A few articles were freely available.
- Mickey Schafer
I recently ran into this in a serious way reviewing facility proposals for a well known synchrotron. Some stuff out of my field and I really just wanted to check whether what was being proposed was novel. But I had no way to do that because I couldn't access the relevant literature.
- Cameron Neylon
Putting in author's name in the advanced filter worked to pull up a single article. It appears that it has to be last name, first name/initial, though there are no immediate instructions for that. In any case, may work for fast retrieval of an individual item for the purposes of checking sources (as opposed to downloading them). Don't know if they have a library or folder system which would be particularly useful for organizations.
- Mickey Schafer
Deep Dyve does have a bookmarking function -- didn't see that until I went to the sign up page. I realize this is not ideal OA by any means, but again, for non-academic practitioners, having a "rental" service is a good solution with significant cost savings compared to individual subscriptions to something like MD Consult.
- Mickey Schafer
see also: http://omicsomics.blogspot.com/2009... - pq: "I've been frustrated on more than one occasion whilst reviewing a paper that I couldn't access their supplementary data, and have certainly encountered this as a reader as well. I've sometimes meekly protested as a reviewer; in the future I resolve to consider this automatic grounds for "needs major revision"." via: http://friendfeed.com/mndoci...
- Bill Hooker
Paper access for a reviewer is indeed a problem! I have to admit, I often just go 'meh' and do a second-rate job, simply to save time. Which is just one of many reasons why for me the status quo of scientific publishing is the worst part of my job.
- Björn Brembs
from iPhone
Meh myself. By the time I put the paperwork in for interlibrary loan, it is activated, payment from my grant is approved, and the rest of the madness the deadline for the review would be way past gone.
- Kubke
Nice, I didn't notice the discussion here had expanded until Bill reshared. @Iddo, does JMB automatically provide instructions for the temporary Scopus account or do they wait for the reviewer to come to them with the problem? Still although there are workarounds like this, a lot of these solutions probably don't work too well with the modus operandi of most scientists... namely,...
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- Shirley Wu
Error level (near 0%) for SwissProt looks interesting. People of protein-protein interaction data claim 2-9% error rate on manually curated sets, and the same level I would expect from SP. Some things are better than I thought ;).
- Pawel Szczesny
Not too bad, but I think its even worse than they do. And evidence codes won't fix this. Manual curation and standards for automatic annotation are in dire need of a revolution, and even if we get that it'll still take years to fix.
- Paul J. Davis
@Paul How would you revolutionise it if all the data is still contained in the relatively unnaccessible journal article?
- Frank
Trust Pawel to see the half full (or 60% full) part of the glass. I agree with Frank though: it is not feasible to go through NR and fix the annotations manually. We just have to accept that NR, TrEMBL and KEGG are (mostly) over-annotating, and remember that when we rely on them when delving into the protein family level.
- Iddo Friedberg
Thanks Iddo. I lost count of how many times annotation errors came up in my discussion with experimentalists who lack experience with such databases. (Not surprisingly, they usually think these errors are negligible, especially when it comes to THEIR proteins.) Now I'll just send them a link to your post...
- Mickey Kosloff
Ask TLS: I vaguely remember a case where some closed-access publisher requested that figures reproduced from a paper published in one of its journals be removed form the author's website. Might have been Science but I am not sure. Anybody has a link?
#smallworld Which reminds me that I must chase up the lead Author of a Paper, nay, Manuscript that Shelley, I and two others have yet to finish and submit to BMC. Prof AG in Milan will be hearing from me soon !
- Graham Steel
yeah ... I never thought about fake structures. I wonder how exactly was fake about them.
- Pedro Beltrao
Built a plausible homology model and shake a bit I would guess...you know of course what will happen now when we discover someone has faked genomics/proteomics data? Omics-gate! The two most overused cliches in media and science finally united together!
- Cameron Neylon
thanks Steve .. at quick glance the common name seams to be last author in many of the papers ... that is even weirder.
- Pedro Beltrao
A posting Kevin Karplus to the pdb-l (possibly) expanding the list to 1bgx 1ay1 1hef 1heg 1sbg 1hps 1hos. Also, it seems that RosettaHoles which assesses core packing did not like 1bgx (it's in the RosettaHoles paper, linked from Kevin's posting. https://lists.sdsc.edu/piperma...
- Iddo Friedberg
From the RosettaHole paper (published online 2-DEC-2008): "Eight of the outliers, (checking for anomalous core packing, IF) (PDB codes 2A01, 1BEF, 1RID, 1Y8E, 1BGX, 1G44, 2QID, 1G40) are from the Murthy group.[9]"
- Iddo Friedberg
What is strangest to me about this story is how did a supervisor get all the other authors to go with the fake results ?
- Pedro Beltrao
Very sad, I saw Warren introduce an early version of PyMol, it was an excellent piece of software for a one man effort. The mailing list announcement is here: https://www.jiscmail.ac.uk/cgi-bin...
- Greg Tyrelle
Ah i see. Nothing on the google yet. He was relatively young too, wasn't he? Sad...
- Shirley Wu
from twhirl
I met him in August and he seemed fine! very depressing
- Rajarshi Guha
He wasn't much older than me and I knew him a bit back in my modeling days, so this really sucks
- Deepak Singh
Very, very sad. Today in my graduate course on RNA one of the students spent most of the class showing us images of the ribosome that he generated with PyMol. The first thing I introduce to the students in this course is how to use PyMol. This is truly a great loss to the community.
- Tom Tullius
so sad. I only interacted with Warren via email, but it was always a pleasure. I greatly admired his support of FOSS, and was inspired by his ground-breaking work in molecular visualization. such sad news.
- tim
So sad--young guy, met him at a conference about 2 years ago. Accomplished so much--his science and entrepreneurship was an inspiration to me.
- Mary Canady
Anyone else interested in helping continue the PyMol codebase?
- Donnie Berkholz
Donnie, certain hope that it doesn't go away
- Deepak Singh
Last I glanced at the PyMol codebase it was actually pretty scary. Sloccount says: Totals grouped by language (dominant language first): ansic: 477951 (85.93%) python: 65182 (11.72%) cpp: 12928 (2.32%)
- Anders Norgaard
I realize I might get slapped for this but with light comes shadow (very Jungian I know). The upside of Warren releasing code as Open Source is that his work can live on and be continued. This is brilliant. The shadow is what about about his young wife that he has left behind? I talked with Warren earlier this year and PyMol was helping him to create a living. But what does his family...
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- Antony Williams
Question: For ages I refused to join Facebook. Now the pressure is on. Should I surrender and join? Do you get an added value from Facebook that you can't get from FriendFeed? What's your take on FB?
Facebook is basically yet another social networking, and not one of the best ones at that. All sorts of privacy and operation issues. You should proabably use it for the same reason I use MS-Word. MS-Word is terrible, but most people I interact with use it, and it would be almost impossible for me to do certain things in my job without resorting to Word once in a while. You'd be happy to know that Facebook is not quite as bad. :)
- Iddo Friedberg
MS-Word wastes my time in many other ways. Yes, I forgot about the spam thing in Facebook.
- Iddo Friedberg
Deleted my account a while ago - tired of deleting invites to install lots of useless applications :). However, I didn't have a huge network on Fb - wrong side of Atlantic.
- Pawel Szczesny
I've had the same question, and I finally decided no. I have enough to keep up with without adding the extremely noisy, cumbersome, and closed facebook to the mix. There's no point joining unless I'm going to participate, and I don't want to get beset by the info-harvesting "apps" that pass for participation on that platform. I think they'll open up, eventually, anyways.
- Mr. Gunn
If you are the "social media" liking kind..jump in..but if you havent yet got an account you probably are not..so dont bother
- Hari
I don't get anything from Facebook on the information and knowledge front, other than staying in touch with old friends who are not anywhere else (and family). But that's not a bad thing
- Deepak Singh
facebook is one of the best current platforms, just behind twitter, with friendfeed as best - the tradeoff for each is excellence of features versus more widespread adoption
- Mike Chelen
Nice post, also applies to wet science- must contact all those collaborators and tell them what happened to th samples they sent...
- Richard Badge
from Nambu
@Chris it's one of those meme-ish pics that are everywhere. Don't know the source.
- Iddo Friedberg
from Android
Hilarious - perfect for hitting the trenches on a Monday morning. I'm always trying to instill in wet lab scientists that bioinformatics approaches are experiments just like any other and should be documented as such. Actually, I think bioinformaticists are often just as cavalier rarely taking good notes of their workflow.
- Todd Harris
You should also claim that you will cure cancer within five years and extend the average human lifespan to 150. Side-effects should include dramatically lowered risk of heart disease and increased sexual pleasure.
- Bill Hooker
I have always found the following useful: "Darling fascist bully boy, give me some more money, you *******. May the seed of your loin be fruitful in the belly of your woman, [Iddo]." - http://en.wikiquote.org/wiki...
- Andrew Lang
is "novel" likewise overused? myself, i'm partial to "boom" a la steve jobs ^_^
- Wladimir Labeikovsky
Non-traditional? Creative? Imaginative? Innovative? But why do I even try when Bill already has the best answer? :-)
- Björn Brembs
Thanks. I accepted all your suggestions. My grant proposal now reads like a Penthouse Forum letter written by a slightly retarded version of Richard Morgan. I hope the reviewers like it.
- Iddo Friedberg
This will be a turning point for your career Iddo, mark my words.
- Bill Hooker
Hopefully you used "bench to bedside" as well
- Deepak Singh
from iPhone
@Deepak, since we're on the Penthouse theme, that does sound like an adult film title now that you mention it..
- Shirley Wu
from twhirl
Automatic negative karma if you use the word "collaboratory". Or cyber. Automatic rejection if you combine the two as cyber-collaboratory.
- Dan Gezelter
from iPhone
Cyber-collaboratory also sounds Penthouse appropriate
- Deepak Singh
from iPhone
Iddo: one approach is to focus on describing the manner in which it is "revolutionary" while using the term itself one time or less
- Mike Chelen
The magic words to use are whatever your evaluation criteria are...
- Donnie Berkholz
Groundbreaking, Breakthrough, Cutting edge... try to avoid words like "bullshit"
- Alexey
You could try starting out the Background and Significance section as follows: "Before I go any further, let me first describe myself and my [collaborator]...We are both in our mid-20s, and are extremely muscular and athletic, with tanned, sculpted bodies, luscious locks of blonde hair, and tight, shapely buns." http://www.theonion.com/content...
- Steve Koch
Continuing along the lines suggested by Steve be sure to include a phrase beginning with "needless to say"
- Maureen
A Text Message-Based Intervention for Weight Loss: Randomized Controlled Trial | Patrick | Journal of Medical Internet Research - http://www.jmir.org/2009...
Published by someone from my old stomping ground, Calit2. In other news, there is a Journal of Medical Internet Research.
- Iddo Friedberg
from Bookmarklet
Sounds very similar to something I was going to try using Twitter to help someone stop smoking. Also reminds me of an initiative in the US where highschoolers were SMSed by friends/relatives encouraging them to finish & not drop out (can't remember what that was called now).
- Andrew Perry
Patent 6,638,908: Crystals of the large ribosomal subunit. Granted October 28, 2003. full text from USPTO. Patent 7,504,486 : Determination and uses of the atomic structures of the large ribosomal subunit and ribosomal subunits and their ligand complexes. Granted March 17, 2009. full text from USPTO.
- Iddo Friedberg
from Bookmarklet
I like the Ella / Louis version better..
- Iddo Friedberg
@Mickey just added Bronksi Beat's vid to the post. Have not seen it in almost 25 (sheesh) years, I actually like it better now than then.
- Iddo Friedberg
Adaptive Complexity is one of my favorite blogs.
- Mickey Schafer
From John Baez quotation within the article: "So, bear in mind that getting tenure is only half the battle: getting tenure while keeping your soul is the really hard part."
- Steve Koch
I sold my soul for a bowl of Ramen in grad school
- Iddo Friedberg
Either computational or crystallography, preferably a mixture. I don't really enjoy NMR. Somewhere in the US -- top pref is Midwest. Second is California or near the East Coast but outside of the Northeast (such as MD, VA, NC, etc).
- Donnie Berkholz
If you prefer Midwest, does Midwest Center for Structural Genomics sound good enough? Lots of smart people, three of five US PIs come from Poland :).
- Pawel Szczesny
I like what people like Michael Chapman are doing w/ cryoEM, fitting higher-resolution structures into it.
- Donnie Berkholz
Need more info from you. What are your personal goals: academia or industry? If the former, the strongest factors that should weigh your choice are the lab's publication record, and the fraction of alumni that went on to academia. A structural genomics center pretty much kills your acedemic carreer, but may open up industry connections. How extensive is your current training? Also, what Chris said.
- Iddo Friedberg
I'd recommend the Baker lab at UW, they're mixed computational and wet(with a bias towards comp.), and do almost anything that has to do with structural biology. Amazing track record and david is a really nice guy.
- Nir London
@Iddo: I don't have "industry vs academia" as a goal. My goal is to do important research that is relevant to improving people's lives, and I can do that anywhere. My current training is my PhD work (1 crystallography project, 1 computational project -- trends in protein structure), and I have no previous postdocs (and no intention of doing more than one). How would you recommend I discover labs with the criteria you cite, other than browsing every university until I stumble over them?
- Donnie Berkholz
@Nir: Yeah, it's a great lab. I spent a week up there on a bit of collaborative work. I'm terribly depressed by the weather in the Pacific Northwest, though, so I need to get away. I'm in Oregon now.
- Donnie Berkholz
"important research that is relevant to improving people's lives" -- is a bit of a naive statement. Choice of lab is derived from personal goals. Would you like to lead a research group after your postdoc? It what setting? How would you fund your research? I third the Baker lab. Other leading labs: Ada Yonath @Weizmann; Tom Steitz @Yale; Andrej Sali @UCSF (computational); Janet Thornton @EBI (computational); Alan Fersht @Cambridge(UK)
- Iddo Friedberg
@Iddo: What's naive about it? My point is that if I'm working on something that's supposedly related to a disease, I don't want the "disease relevance" sections to be a made-up excuse, as they are so often. And I'd rather work on a major problem than on something nobody else cares about (although I realize they are not mutually exclusive).
- Donnie Berkholz
I was not referring to your choice of topic, which is laudable. I was referring to what your personal long-term professional goals are beyond the postdoc. You can work on cancer (per example) running your own group, or you can work on it as an entry-level scientist in a research institute or a company. This long term choice affects the type of postdoc you choose.
- Iddo Friedberg
Slightly offtopic: It seems that often the projects that have "legitimate disease relevance" contribute little to actually curing the target disease, and also fail to significantly advance any basic science. The research with "disease relevance that's actually a made up excuse" can often produce good basic science that down the track contributes to treatments for some disease. Not saying it's always the case, but "pretend disease research" often turns out to be helpful, even if you dont get the same credit.
- Andrew Perry
I also hear great things about David Bakers lab, they produce excellent work, although I don't know him and have never been there. Lynne Regan @Yale is doing some interesting stuff - protein engineering+biophysics+crystallography+NMR .. interests me, but probably not your thing (not directly targeted at any one disease, AFAIK).
- Andrew Perry
My partially redundant reccos in no particular order; David Baker, Charlie Brooks, Ivet Bahar, Jeffrey Skolnick, Wah Chiu, Andrej Sali, Micheal Feig, Tanja Kortemme, Yang Zhang - I think there's no avoiding browsing papers, websites, and ultimately making your own decision
- Adam Kraut
Following Andrew's line of thought, I would say that research that improves people's lives is a thing that happens only in tales entitled "university press release". Science is about understanding nature, not solving world's problems and any attachment to importance of one's own research is going to create lot of frustration ;).
- Pawel Szczesny
"I have no previous postdocs (and no intention of doing more than one)" -- this is smart. Don't get caught in the indentured servant trap. Continuing on with the _realpolitik_, I can't say anything about research but academia is a snakepit. If you want to succeed there, get this straight: it's *not* about the quality of the work, it's about the reputation of the lab you postdoc in, the connections your PI has, and the number of papers you pump out (particularly in C/N/S). [cont'd]
- Bill Hooker
[cont'd] You may want to succeed in order to do worthwhile work -- that's how most of us start out, I think. But in academia, success has much, much less to do with worthwhile work than it should, and that takes a heavy toll. On a happier note, I've seen this work a few times: PhD-->academic postdoc-->industry-->academic PI. An industry track record of deliverables met is gold when the beancounters are trying to figure out if you'll bring in your share of grant money.
- Bill Hooker
Thanks for all the comments! I do realize that basic research can often be extremely valuable down the road. I prefer more direct application, though -- it just gets me more excited. I'll have to look into a few of those recommendations; Andrej Sali had slipped my mind.
- Donnie Berkholz
How has/did your post doc journey played out?
- Sean Seaver
I met André Hoelz recently at a conference. He's at Rockefeller w Gunter Blobel but will start his lab soon in Pasadena. He does beautiful work on the nuclear pore complex, check it out! not immediate medical relevance though (although there's some!)
- Sandra Caldeira
why structural biology ..I would pick up population genetics :-) .Look at the HHMI roster..especially amongst the newer appointees you can definitely find people who mix all the things you have done at grad school well..
- Hari
I don't have any specific recommendations, but if I had to do it all over again, I'd choose someone VERY different from my grad advisor, and also choose someone who's working closely with industry or in translational research.
- Mary Canady
Sean, I ended up at the Mayo Clinic working primarily on structure-based drug design. That had been a long-term goal of mine anyway so I was very happy to find an opportunity to do it during my postdoc.
- Donnie Berkholz
Wow. Thanks for the response and congrats on full filling a long time goal!
- Sean Seaver