Genome U-Plot: a whole genome visualization

Gaitatzes, Athanasios; Johnson, Sarah H.; Smadbeck, James B.; Vasmatzis, George

doi:10.1093/bioinformatics/btx829

Cited by 23 publications

(22 citation statements)

References 20 publications

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“…19 We recently published (1) how MPseq provides comparable sensitivity to the state-of-the-art chromosomal microarray technology for the detection of copy number variations, with the benefit of improved breakpoint resolution; (2) how use of an internal database of polymorphisms is used to mask germline events; and (3) that display of MPseq results with a U plot which provides enhanced resolution of rearrangements and copy number variations than some other commonly used displays. [20][21][22] Germline events were filtered with this mask.…”

Section: Bioinformaticsmentioning

confidence: 99%

Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma

Mansfield

Peikert

Smadbeck

et al. 2019

Journal of Thoracic Oncology

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103

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Introduction: Malignant pleural mesothelioma is a disease primarily associated with exposure to the carcinogen asbestos. Whereas other carcinogen-related tumors are associated with a high tumor mutation burden, mesothelioma is not. We sought to resolve this discrepancy. Methods: We used mate-pair (n ¼ 22), RNA (n ¼ 28), and T cell receptor sequencing along with in silico predictions and immunologic assays to understand how structural variants of chromosomes affect the transcriptome. Results: We observed that inter-or intrachromosomal rearrangements were present in every specimen and were frequently in a pattern of chromoanagenesis such as chromoplexy or chromothripsis. Transcription of rearrangementrelated junctions was predicted to result in many potential neoantigens, some of which were proven to bind patient-specific major histocompatibility complex molecules and to expand intratumoral T cell clones. T cells responsive to these predicted neoantigens were also present in a patient's circulating T cell repertoire. Analysis of genomic array data from the mesothelioma cohort in The Cancer Genome Atlas suggested that multiple chromothriptic-like events negatively impact survival. Conclusions: Our findings represent the discovery of potential neoantigen expression driven by structural chromosomal rearrangements. These results may have implications for the development of novel immunotherapeutic strategies and the selection of patients to receive immunotherapies.

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Section: Bioinformaticsmentioning

confidence: 99%

Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma

Mansfield

Peikert

Smadbeck

et al. 2019

Journal of Thoracic Oncology

Self Cite

103

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“…The Mate Pair whole genome sequencing (MPseq) protocol was utilized to detect structural variants at gene level resolution through specialized larger 2-5 kb fragment tiling of the genome. [31][32][33] One microgram of DNA was applied to MPseq library preparation using the Nextera Mate-Pair Kit (Illumina, CA, FC-132-1001) following the manufacturer's instructions. Libraries were sequenced on the Illumina HiSeq4000 platform at a depth of 4 libraries per lane.…”

Section: Histopathologic Reviewmentioning

confidence: 99%

“…33 Chromosomal copy levels and discordant mapping junctions are visualized on interactive software for genome plots. 31 Please see supplementary materials for more detailed MPseq methods.…”

Section: Histopathologic Reviewmentioning

confidence: 99%

Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine

et al. 2020

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Biliary tract tumors are uncommon but highly aggressive malignancies with poor survival outcomes. Patient-derived xenografts preserve the unique histology and genetic characteristics of the original patient tumor. Successful engraftment is an independent predictor for worse recurrence-free patient survival. Patients with tumors containing tetraploid genomes had worse overall survival. Lay summary Patient biliary tract tumors grown in immunocompromised mice are an invaluable resource in the treatment of biliary tract cancers. They can be used to guide individualized cancer treatment in high-risk patients.

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“…The final step of the algorithm visualizes the results using a novel genome visualization scheme called the genome plot. 26 The results can also be visualized using other common techniques like a linear layout or a circos plot. Each of these steps is provided in more detail in the Supporting Information Methods section.…”

Section: Bmd Structural Variant Pipelinementioning

confidence: 99%

Copy number variant analysis using genome‐wide mate‐pair sequencing

Smadbeck

Johnson

Smoley

et al. 2018

Genes Chromosomes & Cancer

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Copy number variation (CNV) is a common form of structural variation detected in human genomes, occurring as both constitutional and somatic events. Cytogenetic techniques like chromosomal microarray (CMA) are widely used in analyzing CNVs. However, CMA techniques cannot resolve the full nature of these structural variations (i.e. the orientation and location of associated breakpoint junctions) and must be combined with other cytogenetic techniques, such as karyotyping or FISH, to do so. This makes the development of a next-generation sequencing (NGS) approach capable of resolving both CNVs and breakpoint junctions desirable. Mate-pair sequencing (MPseq) is a NGS technology designed to find large structural rearrangements across the entire genome. Here we present an algorithm capable of performing copy number analysis from mate-pair sequencing data. The algorithm uses a step-wise procedure involving normalization, segmentation, and classification of the sequencing data. The segmentation technique combines both read depth and discordant mate-pair reads to increase the sensitivity and resolution of CNV calls. The method is particularly suited to MPseq, which is designed to detect breakpoint junctions at high resolution. This allows for the classification step to accurately calculate copy number levels at the relatively low read depth of MPseq. Here we compare results for a series of hematological cancer samples that were tested with CMA and MPseq. We demonstrate comparable sensitivity to the state-of-the-art CMA technology, with the benefit of improved breakpoint resolution. The algorithm provides a powerful analytical tool for the analysis of MPseq results in cancer.

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Genome U-Plot: a whole genome visualization

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 23 publications

References 20 publications

Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma

Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma

Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine

Copy number variant analysis using genome‐wide mate‐pair sequencing

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