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  1. Jul 2018
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    Fast, scalable prediction of deleterious noncoding variants from functional and population genomic data
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    1. w10a 23 Jul 2018
      Recent efforts to characterize noncoding sequences using high-throughput biochemical assays have produced a wealth of data

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    2. w10a 23 Jul 2018
      Many of these nucleotides appear to fall in cis-regulatory elements

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    3. w10a 12 Jul 2018
      In conceptual terms, the new LINSIGHT method is closely related to our previous fitCons method
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    4. w10a 12 Jul 2018
      Manygeneticvariantsthatinfluencephenotypesofinterestarelocatedoutsideofprotein-codinggenes,yetexistingmethodsforidentifyingsuchvariantshavepoorpredictivepower.Hereweintroduceanewcomputationalmethod,calledLINSIGHT,thatsubstantiallyimprovesthepredictionofnoncodingnucleotidesitesatwhichmutationsarelikelytohavedeleteriousfitnessconsequences,andwhich,therefore,arelikelytobephenotypicallyimportant.LINSIGHTcombinesageneralizedlinearmodelforfunctionalgenomicdatawithaprobabilisticmodelofmolecularevolution.Themethodisfastandhighlyscalable,enablingittoexploitthe‘bigdata’availableinmoderngenomics.WeshowthatLINSIGHToutperformsthebestavailablemethodsinidentifyinghumannoncodingvariantsassociatedwithinheriteddiseases.Inaddition,weapplyLINSIGHTtoanatlasofhumanenhancersandshowthatthefitnessconsequencesatenhancersdependoncelltype,tissuespecificity,andconstraintsatassociatedpromoters.

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