原创力文档sequence and structure signatures of cancer mutation hotspots in protein kinases签名序列和结构蛋白激酶的癌症突变热点.pdfVIP
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sequence and structure signatures of cancer mutation hotspots in protein kinases签名序列和结构蛋白激酶的癌症突变热点
Sequence and Structure Signatures of Cancer Mutation
Hotspots in Protein Kinases
1,2 1 1 3 3
Anshuman Dixit , Lin Yi , Ragul Gowthaman , Ali Torkamani , Nicholas J. Schork , Gennady M.
Verkhivker1,2,4*
1 Graduate Program for Bioinformatics, Center for Bioinformatics, The University of Kansas, Lawrence, Kansas, United States of America, 2 Department of Pharmaceutical
Chemistry, School of Pharmacy, The University of Kansas, Lawrence, Kansas, United States of America, 3 Scripps Genomic Medicine, Department of Molecular and
Experimental Medicine, Scripps Health and The Scripps Research Institute, La Jolla, California, United States of America, 4 Department of Pharmacology, University of
California San Diego, La Jolla, California, United States of America
Abstract
Protein kinases are the most common protein domains implicated in cancer, where somatically acquired mutations are
known to be functionally linked to a variety of cancers. Resequencing studies of protein kinase coding regions have
emphasized the importance of sequence and structure determinants of cancer-causing kinase mutations in understanding
of the mutation-dependent activation process. We have developed an integrated bioinformatics resource, which
consolidated and mapped all currently available information on genetic modifications in protein kinase genes with
sequence, structure and functional data. The integration of diverse data types provided a convenient framework for kinome-
wide study of sequence-based and structure-based signatures of cancer mutations. The database-driven analysis has
revealed a differential enrichment of SNPs categories in function
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