Three years ago, Abel developed and published in the American Journal of Human Genetics an approach to combine the results of several tools aimed at identifying disease-related single nucleotide variants (SNVs). He called the strategy a Consensus Deleteriousness score of SNVs, or Condel. It consisted in computing a weighted average of the scores of five of these tools (SIFT, PolyPhen2, MutationAssessor, LogRE and MAPP). The weights were extracted from the complementary cumulative distributions of the scores of sets of known disease-related and neutral SNVs. He showed that the Consensus score of the five tools outperformed the five individual methods, as well as other approaches to combine them. He presented the Condel of these five tools in one of the first posts of this blog, The making of Condel (CONsensus DELeteriousness Score), published on April 1, 2011.
We’d like to communicate two things: We have released a new version of Gitools which brings new capabilities. With these the new Gitools 2.1.0 in the suitcase, Nuria and myself are traveling to Heidelberg, to give a tutorial session at the Vizualizing Biological data conference (VIZBI).
Two years ago I attended the VIZBI 2012 to present our latest work on and with Gitools, a tool we use to explore interactive heatmaps of genomics data. The days spent in Heidelberg were fruitful and refreshing and after all also were an inspiration to write the review about Visualizing multidimensional cancer genomics data.
We are very honored to announce that we have received funds for a 3-year project from the money raised in the last telethon broadcast La Marató de TV3.
This is an annual television program broadcasted in Catalonia since 1996 which is devoted to diseases that are currently incurable. La Marató has a big repercussion in our country, not only for its ability to raise funds but also because it fulfills the task of informing the public about these diseases, the state of the art of the treatment and the importance of the research to advance in their prevention and cure.
The University Pompeu Fabra has produced a video in which we explain in brief our research. We recorded three versions of the video, one in Catalan, one in Spanish and one in English. The videos are distributed through the UPF youtube channel.
Yesterday I gave a talk at the PRBB Computational Genomics Seminars Series. In that talk I summarized our work of this year in the lab. Basically, we have developed methods to identify cancer driver genes and we have applied them to thousands of tumor resequenced genomes. Here, I leave you the slides, and I summarize the talk below.
Yesterday the paper describing TCGA Pan-Cancer Project was published in Nature Genetics. We’ve had the opportunity to participate in this exciting project and here I would like to explain our experience and contribution to it.
We have been interested for quite a while in the study of patterns of genomics alterations in cancer across tumor types. Thus a project like the TCGA Pan-Cancer provided a unique opportunity to apply our tools and expertise to a unique collection of data.
In the past few years we have developed computational methodologies to identify cancer drivers by analyzing the patterns of somatic mutations across tumors (i.e OncodriveFM and OncodriveCLUST) as well as tools to facilitate the visual exploration of multidimensional cancer genomics datasets (i.e. Gitools, IntOGen, see our review on this topic if you are interested in this), we now had the opportunity to apply those tools to TCGA Pan-Cancer data.
It is now well established that cancer is a collection of mostly genetic diseases. They progress through the accumulation of alterations, such as point mutations in genes that affect mechanisms, often known as the hallmarks of cancer which ultimately confer the altered cell some advantageous properties with respect to neighboring ‘normal’ cells. Decades of intense research on the molecular biology of cancer have delineated many of such hallmarks. Nevertheless, some others have only begun to appear with the advent of large Cancer Genomics initiatives, such as The Cancer Genome Atlas and the International Cancer Genome Consortium.
One of these novel hallmarks has to do with the alteration of general mechanisms of chromatin regulation and maintenance. It is now clear that these mechanisms become altered in one way or another across many tumor types, and that their alteration in principle could lead to the de-regulation of several cellular functions that promote tumorigenesis. With this in mind, we have examined the mutations that occur in chromatin regulatory factors (CRFs) across 4623 tumor samples representing 31 cancer genome re-sequencing projects from 13 anatomical sites. The results of this study have just been published in Genome Biology.
I want to highlight here the main findings of our study.