This paper in Nature from Ian Taylor and Jeff Wrana from U. Toronto present a compelling method for the discrimination and diagnosis of disease states based on the disruption of co-expression patterns with neighbors in a protein interaction network. Typically, the search for cancer biomarkers involves searching for differentially expressed genes which alone can discriminate between different cancer diagnoses. The authors present a method which integrates co-expression and public protein interaction information to show that genes whose protein network neighbors become dysregulated may be used to predict breast cancer outcomes. Their findings support the emerging notion that biomarkers might be improved by focusing on pathways rather than single genes alone. A couple of recent papers from our lab indicate show early signs of promise in this regard. Their results have implications for the systematic discovery of markers in a variety of diseases.

Genetics meets social networks! In a paper today in PNAS Fowler et al compare the topological characteristics of the social networks of MZ and DZ twins and find that some network properties are heritable. This is expanding on some previous work that showed that the −G1438A polymorphism within the promoter region of the 5-HT2A serotonin receptor gene is associated with variation in popularity. The results are interesting, that among teenagers in a various scools, that the number of times a person is named as a friend is heritable (more similar for MZ twins than DZ twins). Adding to this there were another handful of features that were heritable. Overall, this topic is pretty thought provoking, i wonder how many parents would line up for a drug to increase popularity!

I just ran across an interesting paper in Nature on the genetic basis of tumor susceptibility and skin inflammation. The authors use backcrossed mice to identify eQTLs and mapped these onto a network for co-expression based on various skin expression profiles. The expression profiles highlighted skin specific networks such as keratins. Their analysis suggests to me that using a generic co-expression network would not have given them the results that a "local" co-expression network which is based on skin expression which is the system they are interested in. Overall the paper presents an interesting approach for applying networks to eQTL analysis

The-scientist.com released its 2008 salary survey today. There are some interesting tools in there to find out the average pay for professors of different rank in different states (Avg pay for tenured faculty in California is 150K). Somewhat disturbing is the observation that women at the same rank make significantly less than men (23% less pay for women full professors vs men).

Check it out: http://www.the-scientist.com/salarysurvey/

As most reports of this type tend to show that salaries are rising over time in the life sciences fields, how does this jive with reports that there are a glut of postdocs with fewer than 20% finding faculty positions? Isn't this breaking some supply-demand curves? Or does this just mean that theres a glut of inadequately trained PhDs? Maybe this is a job for freakonomics!

ISMB 2008 Toronto, ON- Any other bloggers/readers out there attending this conference want to have an informal meetup? Just give me a shout!

BIO2008 is in town this week in San Diego, where ive been given a press pass. The conference is huge so i'll expect to be attending random sessions, but there are definately a few that are very interesting including algal biofuels, therapeutic gene silencing and personalized medicine. Of course what would any high profile biology conference do without a keynote from Craig Venter. This is by far the most tech saavy conference ive been to with flickr, twitter stream and podcasts.

The BIO2008 blog is at: http://bioontheroad.org/

La Jolla Bioinformatics Conference 2008. This conference features a blend of speakers from both academia and industry with a focus on systems biology/bioinformatics. Because ive talked about most of the academic researchers speaking, ill focus on Industry in bioinformatics.

Steven Hofstadler, VP of research at Ibis Biosciences.
Presented the companies work in determining the identity of an unknown pathogen by primers in a conserved region around a variable region. Such as 23s ribosome which is conserved in many species. They use MS to determine base composition that they use as a signature of a species. The problem of determining base composition from mass measurements is made easier by base complementarity – you know the complement must have the same weight thus reducing your search space for possible bases compositions. From the data he presented this is enough information to distinguish most species of bacteria/pathogens. Using this they were able to identify multiple pathogens in a throat swab sample, which had multiple unknown pathogens. They also have applied this technology toward human and avian flus to determine their subtypes.

Coming away from this talk - someone asked how far do they think this MS-based approach will go. It would seem to me that the time for this is limited with the advent of fast and cheap sequencing technologies-- Its more likely that a hospital or first response site would have a sequencer rather than a mass spec..

Steven Burley, SGX pharmaceuticals
The company is based on Structure based drug discovery. The have a direct spot at the accelerator in Chicago which can run their whole library in 3 days. Their drugs are based on scaffolds that have attachable arms that can be interchanged—providing a modular design for drugs that can be customized using a liquid handler robot. Crystals are created in a pool of a large number of potential leads. Drugs that are tight binders would co-crystallize with the protein providing a potential drug hit. The compounds are optimized based on conformation prediction of drug variants with the known protein structure – a variant of combinatorial chemistry. One of the major boons of this approach is the selectivity, nearly 70% of their compounds only target a single kinase (rather than multiple kinases like many drugs). Showed beginnings of inhibitors targeted to BCR-ABL mutations (such as T315I) which are resistant to Gleevec. Also drugs targeted to MET receptor which activated various kinase cascades and mutations in which implicated in Hereditary papillary renal cell carcinoma.

This was a good talk with some very interesting insight into how drug discovery is done - from target identification to trails. The company was recently hit with some bad news about one of their prize BCR-ABL drug trials (apparently caused toxicity at high dose in trials), but Dr Burley didnt seem to worried about it, they had a couple of other drugs in the pipeline.

Overall it was an entertaining confernce that highlighted the great work done in the area around San Diego - Biotech Beach!