Exploration of Coding and Non-coding Variants in Cancer Using GenomePaint

Zhou, Xin; Wang, Jian; Patel, Jaimin; Valentine, Marc; Shao, Ying; Newman, Scott; Sioson, Edgar; Tian, Liqing; Liu, Yu; Brady, Samuel W.; Flasch, Diane A.; Ma, Xiaotu; Liu, Yanling; Paul, R.; Edmonson, Michael N.; Rusch, Michael; Li, Chunliang; Baker, Suzanne J.; Easton, John; Zhang, Jinghui

doi:10.1016/j.ccell.2020.12.011

Cited by 22 publications

(19 citation statements)

References 42 publications

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“…Notably, GATA2 was the only cis-activated gene in the genomic neighborhood surrounding this deletion ( Supplementary Figures 4A–C ), indicating that GATA2 was the target. Furthermore, in-situ high-through chromosome conformation capture (Hi-C) data for both the B-ALL cell line Nalm6 and neuroblastoma cell line Kelly ( Figure 5C ) from GenomePaint ( 30 ) showed that the deletion overlapped with the boundary of topologically associating domain (TAD) harboring GATA2 . Disruption of the TAD structure by the deletion might aberrantly connect the GATA2 promoter to the active regulatory DNA elements in the adjacent TAD, thus contributing to GATA2 dysregulation in cis.…”

Section: Resultsmentioning

confidence: 99%

“…The focal deletion and the candidate TAD boundary disrupted by the deletion are highlighted in yellow. The whole-genome sequencing and Hi-C data were visualized with GenomePaint ( 30 ) ( https://genomepaint.stjude.cloud/ ).…”

Section: Resultsmentioning

confidence: 99%

“…The protein structure of the in-frame KMT2A-USP2 fusion was visualized with ProteinPaint ( 29 ). The topologically associating domain (TAD) structure from high-through chromosome conformation capture (Hi-C) data from the Nalm6 and Kelly cell line, and the coverage plot of whole-genome sequencing (WGS) data of tumor and matched remission sample of SJALL043839 were visualized with GenomePaint ( 30 ).…”

Section: Methodsmentioning

confidence: 99%

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Aberrant GATA2 Activation in Pediatric B-Cell Acute Lymphoblastic Leukemia

et al. 2022

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GATA2 is a transcription factor that is critical for the generation and survival of hematopoietic stem cells (HSCs). It also plays an important role in the regulation of myeloid differentiation. Accordingly, GATA2 expression is restricted to HSCs and hematopoietic progenitors as well as early erythroid cells and megakaryocytic cells. Here we identified aberrant GATA2 expression in B-cell acute lymphoblastic leukemia (B-ALL) by analyzing transcriptome sequencing data obtained from St. Jude Cloud. Differentially expressed genes upon GATA2 activation showed significantly myeloid-like transcription signature. Further analysis identified several tumor-associated genes as targets of GATA2 activation including BAG3 and EPOR. In addition, the correlation between KMT2A-USP2 fusion and GATA2 activation not only indicates a potential trans-activating mechanism of GATA2 but also suggests that GATA2 is a target of KMT2A-USP2. Furthermore, by integrating whole-genome and transcriptome sequencing data, we showed that GATA2 is also cis activated. A somatic focal deletion located in the GATA2 neighborhood that disrupts the boundaries of topologically associating domains was identified in one B-ALL patient with GATA2 activation. These evidences support the hypothesis that GATA2 could be involved in leukemogenesis of B-ALL and can be transcriptionally activated through multiple mechanisms. The findings of aberrant activation of GATA2 and its molecular function extend our understanding of transcriptional factor dysregulation in B-ALL.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Aberrant GATA2 Activation in Pediatric B-Cell Acute Lymphoblastic Leukemia

et al. 2022

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“…The well-known bioinformatics cloud platform, Galaxy, only provides limited dozens of visualization-based plugins and still lacks adequate optimization for those lightweight biomedical visualization tasks. The visualization module of St. Jude Children’s Research Hospital cloud portal offers 20 JavaScript-based plugins for the interactive cancer genomics visualizations, while the basic scientific graphics is blank [12, 17]. The imageGP merely developed 16 subfunctions for scientific graphics and analysis since 2017 [18].…”

Section: Introductionmentioning

confidence: 99%

Hiplot: a comprehensive and easy-to-use web service boosting publication-ready biomedical data visualization

Miao

Wang

et al. 2022

Preprint

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Modern web techniques provide an unprecedented opportunity for leveraging complex biomedical data generating in clinical, omics, and mechanism experiments. Currently, the functions for carrying out publication-ready biomedical data visualization represent primary technical hurdles in the state-of-art omics-based web services, whereas the demand for visualization-based interactive data mining is ever-growing. Here, we propose an easy-to-use web service, Hiplot (https://hiplot.com.cn), equipping with comprehensive and interactive biomedical data visualization functions (230+) including basic statistics, multi-omics, regression, clustering, dimensional reduction, meta-analysis, survival analysis, risk modeling, etc. We used the demo and real datasets to demonstrate the usage workflow and the core functions of Hiplot. It permits users to conveniently and interactively complete a few specialized visualization tasks that previously could only be done by senior bioinformatics or biostatistics researchers. A modern web client with efficient user interfaces and interaction methods has been implemented based on the custom components library and the extensible plugin system. The versatile output can also be produced in different environments via using the cross-platform portable command-line interface (CLI) program, Hctl. A switchable view between the editable data table and the file uploader/path selection could facilitate data importing, previewing, and exporting, while the plumber-based response strategy significantly reduced the time costs for generating basic scientific graphics. Diversified layouts, themes/styles, and color palettes in this website allow users to create high-quality and publication-ready graphics. Researchers devoted to both life and data science may benefit from the emerging web service.

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“…The increasing scale and complexity of the genomic and clinical data collected for sequenced tumour samples requires flexible analytic platforms suitable for automation 2 , both for the annotation of molecular profiles as well as the concise reporting of such information. While there are visualization tools 13,14 and commercial reporting applications available 7,15,16 , there are few open-source reporting alternatives 17,18 . Despite previous work demonstrating improvements in clinical comprehension of complex genomic data using interactive over static reports 19 , there are currently no open-source web applications for reporting in precision oncology.…”

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confidence: 99%

A platform for oncogenomic reporting and interpretation

et al. 2022

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Manual interpretation of variants remains rate limiting in precision oncology. The increasing scale and complexity of molecular data generated from comprehensive sequencing of cancer samples requires advanced interpretative platforms as precision oncology expands beyond individual patients to entire populations. To address this unmet need, we introduce a Platform for Oncogenomic Reporting and Interpretation (PORI), comprising an analytic framework that facilitates the interpretation and reporting of somatic variants in cancer. PORI integrates reporting and graph knowledge base tools combined with support for manual curation at the reporting stage. PORI represents an open-source platform alternative to commercial reporting solutions suitable for comprehensive genomic data sets in precision oncology. We demonstrate the utility of PORI by matching 9,961 pan-cancer genome atlas tumours to the graph knowledge base, calculating therapeutically informative alterations, and making available reports describing select individual samples.

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Exploration of Coding and Non-coding Variants in Cancer Using GenomePaint

Cited by 22 publications

References 42 publications

Aberrant GATA2 Activation in Pediatric B-Cell Acute Lymphoblastic Leukemia

Aberrant GATA2 Activation in Pediatric B-Cell Acute Lymphoblastic Leukemia

Hiplot: a comprehensive and easy-to-use web service boosting publication-ready biomedical data visualization

A platform for oncogenomic reporting and interpretation

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