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 have worked during the last years on assessing the functional impact of non-synonymous variants (nsSNVs). As a result, we have published two new approaches Condel and transFIC. In this post I would like to clarify the differences between one and the other, and give our recommendations on when each of them should be used.
Several weeks ago we realized we were having problems retrieving the functional impact scores from the MutationAssessor webservice into our condel web server. We immediately corrected the problem by setting up a proxy in our server; nevertheless, we don’t have a clear idea of how long this problem may have been going on. A little later, we discovered that apparently condel scores computed through our web server may have been malformed due to a mismanagement of the response the server obtained from the MutationAssessor webserver. (Note that this problem only affects condel scores computed through the web server, not via the PERL standalone script.)
This year our lab will participate again in the Gulbenkian Training Program in Bioinformatics (GTPB). Abel and Michael will give a 3 days course on Bioinformatics for Integrative Genomics – BIG12, from 7th to 9th May. The course is now open for Inscriptions, and a tentative program can be found here.
GTPB program is very well known for its practical courses on bioinformatics, which have been running since 1999. The courses are eminently practical, including few lectures and many hands on exercises. The groups are small, usually up to 20 attendees, which allows a very intense experience with the topic, the instructors and the rest of attendees. Read the rest of this entry »
We are pleased to announce that we will be giving another practical course on bioinformatics for Integrative Genomics this year. It will take place from November 7-9, 2011, in Oeiras, Portugal, as part of the Gulbenkian Training Programme in Bioinformatics. The course teachers will be Alba Jené and myself from our group. Read the rest of this entry »
We have found two major drawbacks to computational approaches that assess the outcome of non-synonymous SNVs. The first is that there are now too many of them, based on different principles –some using phenomenological scoring functions, some that take advantage of machine learning strategies– but few efforts to make them comparable and integrate their outputs into a consensus that may be readily interpreted and employed by researchers. Our group and others have taken a first step towards the development of approaches to make such consensus possible. We recently developed and presented an approach to compute a Consensus Deleteriousness score (condel) of these computational tools and tested it with five of them. Read the rest of this entry »
When we created IntOGen we had the motivation to convert it into a discovery tool for cancer researchers and a resource that integrates multidimensional OncoGenomics Data. We have now made a new important step in IntOGen project: we have included all somatic mutations detected by the International Cancer Genome Consortium (ICGC) projects. Read the rest of this entry »
On 21-22 June our group is organizing a course open to all reserachers who share our interest on Genomics. It will be similar to the one we gave at the Gulbenkian Institute last november, but this time we will not be focusing on Cancer Genomics but on Genomics in general, so that we can satisfy a broader audience of scientists. Read the rest of this entry »
Our article on a Consensus deleteriousness score of missense Single Nucleotide Variants was published yesterday online and will be included in the April issue of the American Journal of Human Genetics. We want to invite you to read it, and give you a glimpse at how we got the idea. Read the rest of this entry »