@article{MunchelHoangZhaoetal.2015, author = {Munchel, Sarah and Hoang, Yen and Zhao, Yue and Cottrell, Joseph and Klotzle, Brandy and Godwin, Andrew K. and Koestler, Devin and Beyerlein, Peter and Fan, Jian-Bing and Bibikova, Marina and Chien, Jeremy}, title = {Targeted or whole genome sequencing of formalin fixed tissue samples: potential applications in cancer genomics}, series = {Oncotarget}, volume = {6}, journal = {Oncotarget}, number = {28}, issn = {1949-2553}, doi = {10.18632/oncotarget.4671}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6307}, pages = {25943 -- 25961}, year = {2015}, abstract = {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.}, language = {en} } @article{MeierGrawBeyerleinetal.2017, author = {Meier, Richard and Graw, Stefan and Beyerlein, Peter and Koestler, Devin and Molina, Julian R. and Chien, Jeremy}, title = {digit—a tool for detection and identification of genomic interchromosomal translocations}, series = {Nucleic Acids Research}, volume = {45}, journal = {Nucleic Acids Research}, number = {9}, issn = {1362-4962}, doi = {10.1093/nar/gkx010}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-9697}, pages = {e72}, year = {2017}, abstract = {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.}, language = {en} }