Kwon M, Lee S, Berselli M, Chu C, Park PJ. BamSnap: a lightweight viewer for sequencing reads in BAM files. Bioinformatics 2021;Abstract
SUMMARY: Despite the improvement in variant detection algorithms, visual inspection of the read-level data remains an essential step for accurate identification of variants in genome analysis. We developed BamSnap, an efficient BAM file viewer utilizing a graphics library and BAM indexing. In contrast to existing viewers, BamSnap can generate high-quality snapshots rapidly, with customized tracks and layout. As an example, we produced read-level images at 1000 genomic loci for >2500 whole-genomes. AVAILABILITY: BamSnap is freely available at SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Goldman MJ*, Zhang J*, Fonseca NA*, Cortés-Ciriano I*, Xiang Q, Craft B, Piñeiro-Yáñez E, O'Connor BD, Bazant W, Barrera E, Muñoz-Pomer A, Petryszak R, Füllgrabe A, Al-Shahrour F, Keays M, Haussler D, Weinstein JN, Huber W, Valencia A, Park PJ, Papatheodorou I, Zhu J, Ferretti V, Vazquez M. A user guide for the online exploration and visualization of PCAWG data. Nat Commun 2020;11(1):3400.Abstract
The Pan-Cancer Analysis of Whole Genomes (PCAWG) project generated a vast amount of whole-genome cancer sequencing resource data. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we provide a user's guide to the five publicly available online data exploration and visualization tools introduced in the PCAWG marker paper. These tools are ICGC Data Portal, UCSC Xena, Chromothripsis Explorer, Expression Atlas, and PCAWG-Scout. We detail use cases and analyses for each tool, show how they incorporate outside resources from the larger genomics ecosystem, and demonstrate how the tools can be used together to understand the biology of cancers more deeply. Together, the tools enable researchers to query the complex genomic PCAWG data dynamically and integrate external information, enabling and enhancing interpretation.
Gulhan DC, Lee JJ-K, Melloni GEM, Cortés-Ciriano I, Park PJ. Detecting the mutational signature of homologous recombination deficiency in clinical samples. Nature Genetics 2019;51(5):912-919.Abstract
Mutations in BRCA1 and/or BRCA2 (BRCA1/2) are the most common indication of deficiency in the homologous recombination (HR) DNA repair pathway. However, recent genome-wide analyses have shown that the same pattern of mutations found in BRCA1/2-mutant tumors is also present in several other tumors. Here, we present a new computational tool called Signature Multivariate Analysis (SigMA), which can be used to accurately detect the mutational signature associated with HR deficiency from targeted gene panels. Whereas previous methods require whole-genome or whole-exome data, our method detects the HR-deficiency signature even from low mutation counts, by using a likelihood-based measure combined with machine-learning techniques. Cell lines that we identify as HR deficient show a significant response to poly (ADP-ribose) polymerase (PARP) inhibitors; patients with ovarian cancer whom we found to be HR deficient show a significantly longer overall survival with platinum regimens. By enabling panel-based identification of mutational signatures, our method substantially increases the number of patients that may be considered for treatments targeting HR deficiency.
Bohrson CL, Barton AR, Lodato MA, Rodin RE, Luquette LJ, Viswanadham VV, Gulhan DC, Cortés-Ciriano I, Sherman MA, Kwon M, Coulter ME, Galor A, Walsh CA, Park PJ. Linked-read analysis identifies mutations in single-cell DNA-sequencing data. Nature Genetics 2019;51:749-754.Abstract
Whole-genome sequencing of DNA from single cells has the potential to reshape our understanding of mutational heterogeneity in normal and diseased tissues. However, a major difficulty is distinguishing amplification artifacts from biologically derived somatic mutations. Here, we describe linked-read analysis (LiRA), a method that accurately identifies somatic singlenucleotide variants (sSNVs) by using read-level phasing with nearby germline heterozygous polymorphisms, thereby enabling the characterization of mutational signatures and estimation of somatic mutation rates in single cells.
Kerpedjiev P, Abdennur N, Lekschas F, McCallum C, Dinkla K, Strobelt H, Luber JM, Ouellette SB, Azhir A, Kumar N, Hwang J, Lee S, Alver BH, Pfister H, Mirny LA, Park PJ, Gehlenborg N. HiGlass: web-based visual exploration and analysis of genome interaction maps. Genome Biol 2018;19(1):125.Abstract
We present HiGlass, an open source visualization tool built on web technologies that provides a rich interface for rapid, multiplex, and multiscale navigation of 2D genomic maps alongside 1D genomic tracks, allowing users to combine various data types, synchronize multiple visualization modalities, and share fully customizable views with others. We demonstrate its utility in exploring different experimental conditions, comparing the results of analyses, and creating interactive snapshots to share with collaborators and the broader public. HiGlass is accessible online at and is also available as a containerized application that can be run on any platform.
Lee S*, Lee S*, Ouellette S, Park W-Y, Lee EA**, Park PJ**. NGSCheckMate: software for validating sample identity in next-generation sequencing studies within and across data types. Nucleic Acids Res 2017;Abstract

In many next-generation sequencing (NGS) studies, multiple samples or data types are profiled for each individual. An important quality control (QC) step in these studies is to ensure that datasets from the same subject are properly paired. Given the heterogeneity of data types, file types and sequencing depths in a multi-dimensional study, a robust program that provides a standardized metric for genotype comparisons would be useful. Here, we describe NGSCheckMate, a user-friendly software package for verifying sample identities from FASTQ, BAM or VCF files. This tool uses a model-based method to compare allele read fractions at known single-nucleotide polymorphisms, considering depth-dependent behavior of similarity metrics for identical and unrelated samples. Our evaluation shows that NGSCheckMate is effective for a variety of data types, including exome sequencing, whole-genome sequencing, RNA-seq, ChIP-seq, targeted sequencing and single-cell whole-genome sequencing, with a minimal requirement for sequencing depth (>0.5X). An alignment-free module can be run directly on FASTQ files for a quick initial check. We recommend using this software as a QC step in NGS studies. AVAILABILITY:

Yang L, Luquette LJ, Gehlenborg N, Xi R, Haseley PS, Hsieh C-H, Zhang C, Ren X, Protopopov A, Chin L, Kucherlapati R, Lee C, Park PJ. Diverse mechanisms of somatic structural variations in human cancer genomes. Cell 2013;153(4):919-29.Abstract

Identification of somatic rearrangements in cancer genomes has accelerated through analysis of high-throughput sequencing data. However, characterization of complex structural alterations and their underlying mechanisms remains inadequate. Here, applying an algorithm to predict structural variations from short reads, we report a comprehensive catalog of somatic structural variations and the mechanisms generating them, using high-coverage whole-genome sequencing data from 140 patients across ten tumor types. We characterize the relative contributions of different types of rearrangements and their mutational mechanisms, find that ~20% of the somatic deletions are complex deletions formed by replication errors, and describe the differences between the mutational mechanisms in somatic and germline alterations. Importantly, we provide detailed reconstructions of the events responsible for loss of CDKN2A/B and gain of EGFR in glioblastoma, revealing that these alterations can result from multiple mechanisms even in a single genome and that both DNA double-strand breaks and replication errors drive somatic rearrangements.

Gehlenborg N, Noble MS, Getz G, Chin L, Park PJ. Nozzle: a report generation toolkit for data analysis pipelines. Bioinformatics 2013;29(8):1089-91.Abstract

SUMMARY: We have developed Nozzle, an R package that provides an Application Programming Interface to generate HTML reports with dynamic user interface elements. Nozzle was designed to facilitate summarization and rapid browsing of complex results in data analysis pipelines where multiple analyses are performed frequently on big datasets. The package can be applied to any project where user-friendly reports need to be created. AVAILABILITY: The R package is available on CRAN at Examples and additional materials are available at The source code is also available at SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Kong SW, Hwang K-B, Kim RD, Zhang B-T, Greenberg SA, Kohane IS, Park PJ. CrossChip: a system supporting comparative analysis of different generations of Affymetrix arrays. Bioinformatics 2005;21(9):2116-7.Abstract

SUMMARY: To increase compatibility between different generations of Affymetrix GeneChip arrays, we propose a method of filtering probes based on their sequences. Our method is implemented as a web-based service for downloading necessary materials for converting the raw data files (*.CEL) for comparative analysis. The user can specify the appropriate level of filtering by setting the criteria for the minimum overlap length between probe sequences and the minimum number of usable probe pairs per probe set. Our website supports a within-species comparison for human and mouse GeneChip arrays. AVAILABILITY: