Notes from the biomass

Everyone is using tiling arrays these days but the quality of results is still hard to judge even for the most experienced people in the field. Designs differ in type of the oligo density, oligo length, selection algorithms and experimental procedures. On top of that, several analysis procedures claim to be superior over each other. Eight groups performed independent evaluations of tiling arrays for the human genome from the major vendors (Affymetrix, NimbleGen and Agilent) and report their findings in Genome Research, on February 7th, 2008. As the scientists had no knowledge about the PCR products that were spiked in the sample, this is an blind evaluation and thus much more powerful than the typical validations using real time PCR.

The overall results are a sobering: only 50% of the sequences selected were consistently detected at10% FDR. This is not to be taken literally as the majority of the missed samples were present in low numbers only (1.25 to 4 fold) and we do not have good data for the true fold changes in these experiments.

All three vendors supported this study and employ a good number of the authors. In that light, it is no surprise that the study does not report major quality differences between the chips. They do report that Affymetrix arrays require more repetitions to reach the same quality of the results but are of lower price (conveniently tabulated in the paper). No method performs well in the low concentration regime, although Agilent and Nimblegen arrays look a little better at it. I certainly don’t want to imply that the affiliations biased the results of this study (this is the internet after all). On the contrary, this is a very useful collaboration between chip vendors and technology leaders in academia. But read it before the next sales person in the chip business knocks on your door or you want to build trust in a particular data set.

Konrad was the first this morning to hint at release of Venters effort of providing  environmental sequencing samples from the world oceans. The data is backed by several papers in PLoS Biology and the new camera database. Other bloggers have followed and the main stream media will pick it up soon.
What to add on a busy day like today? The results might not breathtaking but that was as true for the release of the release of the human genome project back in 2000. Sequencing the human genome was a necessity - but the environmental samples provide a complete new picture of our planet, even if our initial view is warped and noisy and our ways of understanding the data is limited.

The newly founded company Metaweb recently announced Freebase, an effort to organize the world’s information by creating meaningful connections between the different data sources. The data base will be released under a Creative Commons by-attribution license.
The major difference to Google Base from what little I can see at this point is that the company actively takes place in integrating the different data and creating a meaningful way to navigate rather than search it. Freebase already incorporates Wikipedia and other smaller projects and should allow future content to be connected to this resource in a controlled manner. However, as the database is early alpha and only open by invitation, it’s premature to discuss the use on hard scientific data.
There’s more on the matter in Konrad’s post and comprehensive coverage on bbgm.

Update: An informative sneak preview and the news that BioMedCentral content will be incorporated.

Rob Carlson from the synthesis blog and author of the New Economy forthcoming book “Biology is Technology” suggests to use Open Biology rather than Open Source Biology and admits in a recent post:

Despite unleashing the phrase “Open Source Biology” on the world six years ago, at this point I no longer know what Open Source Biology might be. Perhaps Drew Endy still has a useful definition in mind, but as I try to understand how to maintain progress, improve safety, and keep the door open for economic growth, I think the analogy between software and biology just doesn’t go far enough. Biology isn’t software, and DNA isn’t code.

The following analysis highlights why we have not seen biohackers tinkering with bugs as we have hackers tinkering with computers abound today.

The tiny, neat Firefox extension called Serchilo deserves more than a del.icio.us entry. It is useful to have Crtl-k to get to the beloved search box but I don’t always want to search in Google and selecting a different search engine was surprisingly inconvenient. After the installation of the Serchilo plugin, the whole procedure is shortened to supply a keyword (’g’ in the case of Google) to the query to address the server in question. 200 different search engines were already configured, including Pubmed; I just added HubMed, which worked painlessly too. Serchilo can take more than just single arguments and therefore ‘dbt Hamburg, Berlin, 7:00, 12.4′ yields sensible answers. Useful!

The Altar des Alltags is a shrine currently installed in Munich by assorted Riesenmaschine followers to address our everyday gods. My non-German speaking readers are invited to pray to the Pantheon of Communication to catch the gist of the powers of the God for the Simple Solution of Complex Problems, the God for Forgotten Passwords and Merciful Amnesia, and their colleagues or just bow down, all of which can be done conveniently over the internet.

Sequencing a eukaryote organism apparently needs to pay back the effort with the initial publication, just like Hollywood blockbuster needs to bring its money on the opening weekend.
The problem is just that there are rarely exploitable surprises found in the sequence. At best, we bump into are harsh reminders of our ignorance. The genome of Mycobacterium tuberculosis told us that the PE/PPE genes, a large group of species-specific proteins were missed in 100 years of research on the bug. And remember that the main message of the human genome was that we had fewer genes than expected. Breaking news: estimates were wrong.
So, do the 222 Toll-like receptors found in the sea urchin’s genome (special Science issue) tell us much about the development of innate immunity? It rather shows that it will be nearly impossible to make simple inferences for these systems of the sea urchin and metazoans – which is certainly highly interesting yet somewhat unpleasant.

The conclusions of the review of the TLRs in Science include the following.
First, this genome sequence significantly refines our understanding of deuterostome immunity.
Which is a nice way of saying that many previous assumptions need to be jettisoned. Sequencing a genome is a good way of supplementing our lack of understanding with another myriad of unanswered questions - and a necessary framework to answer them. But didn’t yesterday’s ignorance feel more knowledgeable when the question/answers ratio suddenly increases dramatically?

N.B. Check Jonathan Eisen’s comment on justifying the efforts of sequencing.

Youtube links were about the last thing I thought I’d ever blog. But the lab tour of the Knight & Eddy labs at the MIT are highly suitable for Friday nights and Monday mornings alike. [via]

Nature Biotech has opened a new section, Community Consultation, which aims to involve the scientific community in the development of standards for publications. The first manuscript for review discusses The Minimum Information required for reporting a Molecular Interaction Experiment (MIMIx).

The authors comprise many important people in the interacting proteins field, both experimentalists and bioinformaticians associated with the development of databases such as DIP, BOND and Intact. One important focus is to enforce unique identifiers for biomolecules; I was pleased to see that the experimental role (such as “bait” in a biochemical purification experiment) is enforced too, as it was missing from many databases and is often neglected in bioinformatics network analysis.

The bioinformatics community will benefit from these standards most. Let’s hope that all publishers will enforce them consistently.
[Via Pedro Beltrao. Nature could really give this broader coverage, they should be proud of it.]

Any sufficiently advanced technology is indistinguishable from magic as long as you don’t use it in your everyday work. In the sciences, there is hardly anything left that I would consider magic devices - instruments that fascinate me because they contradict my daily macroscopic experience. Mass spectrometers are a notable exception. Working in the vicinity of these instruments for several years and probably having understood how some of them work, the results these instruments deliver still fascinate me.

There are other applications to mass spectrometry in biology than identifying proteins, I sometimes have to remind myself. In a recent article in Journal of Biology Claude Lechene and colleagues describe a new instrument that uses stable isotope mass spectrometry for imaging cells in unlabeled samples.

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