By Samuel Payne

AGBT, Marco Island 2010

I just got back from AGBT in Marco Island, Florida and I am still in awe. As noted in the name, this conference highlights advances in both genome biology and technology. The biology seemed to be very human genome centric. Many of the talks presented full genome sequences of cancer genomes or familial cohorts. Some of the numbers that people threw around were shocking. It was only a short time ago that Craig Venter came out with the first personal genome, and now sequencing centers like Washington University in St. Louis and the Broad are talking about sequencing hundreds of human genomes in a year. I was really impressed by a talk from Wash-U where they sequenced 4 exomes for Miller’s syndrome – two normal parents and two affected children - and discovered the causative gene. They were also very honest about their efforts not being as readily successful in a variety of other Mendelian autosomal recessive traits.

One of the more interesting fallouts from all this sequencing is that everyone is submitting to dbSNP; I think that soon nearly every base will have a SNP. Unfortunately people are currently using dbSNP to filter out candidate SNPs for their study. Their logic runs something like, “If it’s in dbSNP then it must be benign.” You can easily see that with the sequencing of several hundred cancer genomes, this proposition will no longer hold. dbSNP will hold a vast array of deleterious SNPs. What it needs to transform into is not just a database of ‘Chr17:2345656 A->T’, but rather something that keeps track of frequency and phenotype. Also there was a discussion about false-discovery rates, and how to keep databases clean. Some of these studies were going to submit 18 million new SNPs, with a 10% FDR. That’s 2 million false positives :(

The technology portion of the conference was amazing. There were new instruments being rolled out by numerous companies, and they were all promising. I loved sitting and listening to the clever new set-ups. There were several single molecule sequencers which I am very excited for – because we can hopefully get past metagenomic pools and on to metagenomic genomes.

I was lucky to be chosen as a presenter in the Genome Informatics session on Thursday evening. There were lots of talks about RNA-seq and getting more out of your sequencing data. So I felt like a bit of an outsider not talking about sequencing. My presentation was on proteogenomics, which uses proteomic data to improve genome annotation. Then major thrust for this audience is that genome annotation is far from perfect, and proteomics evidence can reveal many novel proteins in every genome that I’ve come across. I think that as biology expands past E. coli and B. subtilis into the vastness of genome diversity, we are seeing genes that look nothing like we’ve ever imagined. Rather, as I point out in the talk, we are often NOT seeing these new genes because gene predictors fail to recognize them. I’ve attached the slides to the post for your viewing pleasure (Payne.AGBT.2010.pptx). Let me know what you think.