This week’s SNPpets illustrate that everyone’s back in the saddle after the holidays with plenty of chatter. New and updated databases, 工具, and other news abound. The financial threat to well known databases like FlyBase, 麦肯锡, OMIM, Reactome, UniProt, 等–took my breath away though. Loved the RStudio cheat sheet. 和 ProteinPaint lollipop plots of mutations looks great.
The sequence data tsunami begins to crash into the shore, at the feet of clinicians and patients who want answers and treatment directions. But sometimes the tsunami is washing in debris. As the amount of sequence and variation information grows, some of it comes without clear evaluations of the impacts. Some of it comes with conflicting information. And some of it comes in wrong.
Attempting to wrangle the information into useful understanding and treatments with standardized descriptions, the team building the ClinGen resources published a paper last week that details their efforts. The paper describes their history and goals, and how they are moving to get to a point where they have useful information for and from patients, their doctors, testing labs, and researchers. Because of the different needs of different groups, there are several moving parts to the overall ClinGen collection.
In addition to the paper–and several related articles in this NEJM special report–there are videos on their site that tackle different aspects of the ClinGen projects. I’m going to highlight one of them here as the Tip of the Week, but you should also check out the others that are available on their webinars page or their YouTube频道. This video shows the Dosage Sensitivity Map features.
This video provides some of the history and framework for the ClinGen efforts, and then also introduces one of the tools that they have made available, a dosage sensitivity map. This piece focuses on “evidence based reviews of dosage sensitivity”, and they indicate haploinsufficiency losses of regions, and triplosensitivity duplications of regions. They describe a scoring system they use to rank structural variations (CNVs中, 颗卫星), and their curation of the evidence to support or to refute dosage sensitivity. They also note that their process is conservative, and you should keep that in mind as you consider the their team’s review of the evidence. But they are definitely open and interested in feedback and they hope you will contact them if you have a different understanding from their posted evaluations.
To follow along with the video, use this site to explore the features of this part of the ClinGen tool set: http://www.ncbi.nlm.nih.gov/projects/dbvar/clingen/. But you can also just click their example genes–例如, the ZEB2 link shows you a typical page with the score information, links to other resources, and a genome viewer right on the page. But you can also choose to look at external browsers at NCBI, Ensembl, or UCSC. I clicked the UCSC基因组浏览器 one to see how it displayed, and they automatically present to you tracks with the relevant ClinGen data loaded.
In other tips I’ll talk about other pieces of the infrastructure that they are building or coordinating with. Some we’ve talked about before–you can see a previous tip that included the ClinVar resource at NCBI that is foundational to the ClinGen suite and is discussed in their paper as well. They also note the importance of the data from OMIM, and how their mutual efforts are providing important feedback loops to be alerted to needed updates. ClinGen also employs the Human Phenotype Ontology 这 keeps coming up at OpenHelix 最近. Another important piece to this is the standards for naming variants that were recently described by the American College of Medical Genetics and Genomics (paper linked below).
ClinGen, and the various component tools within, are worth looking at, and contributing to, as we try to move more and better information to the clinic for patients and doctors to use effectively. Steven Salzberg has a take on the value of ClinGen here: 17% Of Our Genetic Knowledge Is Wrong.
It’s also very possible that some really important things will happen in the database–new submissions, changes to the status of a variant–that will occur before any papers come out about it. Or it is even possible that a paper never will come out about it. Spend some time learning about the features; I think it will be worth the time.
Richards, 学, 阿齐兹, 全, 芭蕾舞, 学, Bick, 四, Das, 学, Gastier-Foster, j的, Grody, 瓦特, Hegde, 米, Lyon, 大肠杆菌, 斯佩克特, 大肠杆菌, Voelkerding, 光, & 雷姆, ħ. (2015). Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology 医学遗传学, 17 (5), 405-423 分类号: 10.1038/gim.2015.30