MARC Record from marc_columbia

LEADER: 03065cam a22003853i 4500
001 13598484
005 20201105181807.0
006 m o d
007 cr |n||||a||||
008 181105s2018 nyu|||| om 00| ||eng d
035 $a(OCoLC)1074384749
035 $a(OCoLC)on1074384749
035 $a(NNC)ACfeed:legacy_id:ac:cfxpnvx0nj
035 $a(NNC)ACfeed:doi:10.7916/D8Z625XQ
035 $a(NNC)13598484
040 $aNNC$beng$erda$cNNC
100 1 $aChen, Chen.
245 14 $aThe generation and phenotypic effect of human genetic mutations /$cChen Chen.
264 1 $a[New York, N.Y.?] :$b[publisher not identified],$c2018.
336 $atext$btxt$2rdacontent
337 $acomputer$bc$2rdamedia
338 $aonline resource$bcr$2rdacarrier
300 $a1 online resource.
502 $aThesis (Ph.D.)--Columbia University, 2018.
500 $aDepartment: Biological Sciences.
500 $aThesis advisor: Yufeng Shen.
520 $aMutations cause genetic variations among cells within an individual as well as variations between individuals within a species. It is the fuel for evolution and contributes to most human diseases. Despite its importance, it still remains elusive how mutagenesis and repair shape the mutation pattern in the human genome and how to interpret the impact of a mutation with respect to its ability to cause disease (referred to as pathogenicity). The availability of large-scale genomic data provides us an opportunity to use machine learning methods to answer these questions. This thesis is composed of two parts. In the first part, a single statistical model is applied to both mutations in germline and soma to compare the determinant factors that influence local mutation. Notably, our model revealed that one determinant, expression level, has an opposite effect on mutation rate in the two types of tissues. More specifically, somatic mutation rates decrease with expression levels and, in sharp contrast, germline mutation rates increase with expression levels, indicating that the DNA damage or repair processes during transcription differ between them.
520 $aIn the second part, we developed a new neural-network-based machine learning method to predict the pathogenicity of missense variants. Besides predictors commonly used in previous methods, we included additional predictors at the variant-level such as the probability of being in protein-protein interaction interface and gene-level such as dosage sensitivity and protein complex formation probability. To benchmark real-world performance, we compiled somatic mutation data in cancer and germline de novo mutation data in developmental disorders. Our model achieved better performance in prioritizing pathogenic missense variants than previously published methods.
653 0 $aBioinformatics
653 0 $aComputer science
653 0 $aMutation (Biology)
653 0 $aHuman genetics--Variation
653 0 $aMachine learning
856 40 $uhttps://doi.org/10.7916/D8Z625XQ$zClick for full text
852 8 $blweb$hDISSERTATIONS