In Nature this week, members of the Encyclopedia of DNA Elements, or ENCODE, project provide an overview of the effort, which involved the systematic mapping of regions of transcription, transcription factor association, chromatin structure, and histone modification. From this work, investigators were able to assign biochemical functions to 80 percent of the genome, "in particular outside of the well-studied protein-coding regions." On top of this, they found that many discovered candidate regulatory elements are physically associated with each other and with expressed genes, "providing new insights into the mechanisms of gene regulation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research."
Also in Nature, ENCODE's lead analysis coordinator and European Molecular Biology Laboratory associate director Ewan Birney published a comment piece on the program, noting that important lessons applicable to all scientific consortia were learned along the way. Importantly, he wrote, large-scale consortia need a clear structure that is "transparent to everyone involved" and is "flexible enough to change over time and to encompass multiple sources of funding." At the same time, codes of conduct are necessary to address inevitable "misunderstandings and clashes [that] can arise because of cultural differences" and to ensure the proper sharing of work and credit among consortia participants. "ENCODE is a foundational data set for understanding the human genome," he concluded. "I am proud of what we have delivered, but there are things we could have done better. I hope that other groups can learn from our experience."
Meanwhile, in Nature Genetics, an international team of researchers led by the Max Planck Institute publishes the results of two independent studies that identified potential therapeutic targets for small cell lung cancer following the sequencing the exomes from 82 tumor samples. Between the data generated from the two studies, investigators found 22 significantly mutated genes, including genes that encode kinases, G-protein coupled receptors, and chromatin modifying proteins. They also identified SOX2 amplification in almost 30 percent of the samples, suggesting a key role for the gene in small cell lung cancer.