TY - JOUR A1 - Munchel, Sarah A1 - Hoang, Yen A1 - Zhao, Yue A1 - Cottrell, Joseph A1 - Klotzle, Brandy A1 - Godwin, Andrew K. A1 - Koestler, Devin A1 - Beyerlein, Peter A1 - Fan, Jian-Bing A1 - Bibikova, Marina A1 - Chien, Jeremy T1 - Targeted or whole genome sequencing of formalin fixed tissue samples: potential applications in cancer genomics JF - Oncotarget N2 - Current genomic studies are limited by the poor availability of fresh-frozen tissue samples. Although formalin-fixed diagnostic samples are in abundance, they are seldom used in current genomic studies because of the concern of formalin-fixation artifacts. Better characterization of these artifacts will allow the use of archived clinical specimens in translational and clinical research studies. To provide a systematic analysis of formalin-fixation artifacts on Illumina sequencing, we generated 26 DNA sequencing data sets from 13 pairs of matched formalin-fixed paraffin-embedded (FFPE) and fresh-frozen (FF) tissue samples. The results indicate high rate of concordant calls between matched FF/FFPE pairs at reference and variant positions in three commonly used sequencing approaches (whole genome, whole exome, and targeted exon sequencing). Global mismatch rates and C·G > T·A substitutions were comparable between matched FF/FFPE samples, and discordant rates were low (<0.26%) in all samples. Finally, low-pass whole genome sequencing produces similar pattern of copy number alterations between FF/FFPE pairs. The results from our studies suggest the potential use of diagnostic FFPE samples for cancer genomic studies to characterize and catalog variations in cancer genomes. KW - cancer genomics KW - FFPE DNA KW - whole exome sequencing KW - whole genome sequencing KW - copy number alteration Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-6307 SN - 1949-2553 VL - 6 IS - 28 SP - 25943 EP - 25961 ER - TY - JOUR A1 - Meier, Richard A1 - Graw, Stefan A1 - Beyerlein, Peter A1 - Koestler, Devin A1 - Molina, Julian R. A1 - Chien, Jeremy T1 - digit—a tool for detection and identification of genomic interchromosomal translocations JF - Nucleic Acids Research N2 - Structural variations (SVs) in genomic DNA can have profound effects on the evolution of living organisms, on phenotypic variations and on disease processes. A critical step in discovering the full extent of structural variations is the development of tools to characterize these variations accurately in next generation sequencing data. Toward this goal, we developed a software pipeline named digit that implements a novel measure of mapping ambiguity to discover interchromosomal SVs from mate-pair and pair-end sequencing data. The workflow robustly handles the high numbers of artifacts present in mate-pair sequencing and reduces the false positive rate while maintaining sensitivity. In the simulated data set, our workflow recovered 96% of simulated SVs. It generates a self-updating library of common translocations and allows for the investigation of patient- or group-specific events, making it suitable for discovering and cataloging chromosomal translocations associated with specific groups, traits, diseases or population structures. Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:526-opus4-9697 SN - 1362-4962 VL - 45 IS - 9 SP - e72 ER -