Oncogenic pathway signatures in human cancers as a guide to targeted therapies in this month's Nature by Bild et al. describes a fairly comprehensive report on how the signature of expression of a group of genes (rather than genes acting individually as has been done in the past) can predict outcomes and subtypes of various cancers. Really here 'pathways' seem to be groups of genes whose expression is most correlated with a cancer outcome and then they are reduced to their dominant principal components. The principal components are used to classify and predict cancer outcomes. To test this approach they move from human to mouse models for these types of cancer and find that the same group of genes in mouse is diagnostic of cancer subtypes. Moving forward they use this approach for identifying metagenes (pathways) involved in cancer survival time, and drug sensitivity.
Overall the paper was very interesting and really showed a great in-depth validation of a bioinformatic approach that was previously published.
The mouse work was a very interesting method of validation that was particularly convincing.

Genome annotation errors in pathway databases due to semantic ambiguity in partial EC numbers, by Green and Karp in NAR, is crucial reading for people in the bioinformatics community. It highlights (in the context of pathway databases) two errors which are potential pitfalls for bioinformaticians: erroneously interpreting other researchers' data and not fully understanding data types when making automated curation software.

The paper points out a system-wide error in pathway databases like
KEGG in dealing with partial EC numbers (e.g. 1.1.1.-). The two
meanings of this notation are confused in the databases, and multiple genes are often assigned to incorrect functions as a result. Their
results show that only 28% of genes with a partial EC number are
correctly annotated in KEGG. They propose a new annotation for
partial EC numbers to resolve the ambiguity.

Overall the paper is a quick read, fairly controversial in our group,
but instructive.

*written by a guest reviewer

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PSB 2006
Eric Meslin, "The Moral Status of U.S. Science and Science Policy: Lessons from the Stem Cell Research Wars"

The scheduling of this talk was actually quite lucky considering things going on in Korea right now over the faked papers. They are now saying that all papers concerning human stem cells by Hwang Woo-suk were faked. However, Dr. Meslin really skirted this subject besides pretty much saying that it was unethical. It would have been a lot more interesting to me if he had speculated on the effect this would have on international stem cell policy.
The talk really focused on the similarities between the stem cell policies of the Bush and Clinton administrations. Dr. Meslin was the head of the Bioethics committee appointed by Clinton, so he spoke from firsthand experience. The Clinton administration came out and said that they do not support cloning within two days of the Thompson 1998 Science paper (overview here).
The Bush administration has maintained the same position as Clinton, and that's where we have stayed. The lesson he points to from this is that stem cells are not a party issue but rather a conservative and liberal issue. And even beyond this it's almost out of the hands of the public at large. Polling suggests that 54% of people in the US support pursuing stem cell research. Why this disparity?
He points to failures in government organization. For example, the advisors for science policy are spread out over many departments (can you believe this: The defense department has the most committees concerning national scientific policy!) and this leads to leadership without responsibility. Also, he points out that policy is driven by the budget, and when budgets are done year by year there is no consistency in what is getting funded.

Interestingly, he also said that in other countries the stem cell position is fickle. In Spain all it took was a train bombing, and with the resulting regime change came a change in the national position on stem cell research.
All in all this was an interesting talk. It had nothing to do with bioinformatics, but it was interesting to hear about the possible future of stem cell research in our own country.

PSB 2006
Michael Ashburner, "Ontologies for biologists - A community model for the annotation of genomic data"
One of the originators of the GO ontology, Dr. Ashburner talked about the intial planning and development of the GO ontology and how it (and everything in bioinformatics) should follow the "Manifesto of liberation of bioinformatics":
-Be open source.
-Use open standards.
-Make data and code available without constraint.
-Involve your community.

He also noted that in the near future there will be links between the three main categories in the GO ontology (geneontology.org) meaning there will be interrelationships between molecular functions, biological processes, and locations. For me, this means more headache for developing methods that must utilize the now more complex (interrelated) heirarchy of the ontology. It seems from this talk that the future is more and more ontologies that are all linked together somehow. He mentions that there are many specialized ontologies that are popping up that augment GO. Think things like neuro ontology and ligand ontology (author's ideas not Dr. Ashburner's); moreover these ontologies are linked and launched through efforts like the national center for biomedical ontology.

Perhaps the most successful type of new ontology (well I'll assume it's the most successful because it's the only other one he got into) is Sequence Ontology or (SO). Here sequences are annotated with different features for different locations on the sequence with a defined ontological heirarchy. He mentions attributes encompassing sequence attributes, mutational consequences, and chromosomal variation.
All in all it was an interesting talk about the future of biological ontologies, which, in my view, is a pretty much thankless job but very important to the field. Think over 1000 citations on Scholar.

Stay tuned this week as bioinfblog reports from the Pacific Symposium on Biocomputing 2006 (PSB site) from gorgeous Maui! There are keynotes from Dr. Michael Ashburner who is credited with setting up the GO ontology and Gene Ontology consortium as well as Dr. Eric M. Meslin who will speak about the effects of the U.S. policy on stem cell research. The talk from Dr. Melsin should be interesting considering the recent Korea debacle.