Genome Modeling System: A Knowledge Management Platform for Genomics

Abstract

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms.

A Phase I Trial of BKM120 (Buparlisib) in Combination with Fulvestrant in Postmenopausal Women with Estrogen Receptor–Positive Metastatic Breast Cancer

“…All sequence data were processed using the Genome Modeling System (GMS) (12, 13) reference alignment, somatic variation, and clinical sequencing pipelines. Briefly, raw sequence data were aligned to the human reference genome (build 37) with bwa v0.5.9 (14) using default parameters except for ‘-t 4 -q 5’.…”

“…Small insertions and deletions (indels) were detected by taking the union of four variant callers: GATK somatic indel (15), Pindel v0.5, Varscan v2.2.6, and Strelka v0.4.6.2 all using default parameters except for ‘isSkipDepthFilters = 1’ for Strelka. All variants were manually reviewed using the Integrated Genome Browser (IGV) (19) as previously described (13). All SNVs and indels passing manual review were annotated to determine their predicted effect on amino acid sequences using the GMS transcript annotator and known transcript models from Ensembl (version 74) (20).…”

Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B-lymphoblastic leukemia

“…Since the second relapse sample occurred after an allograft from a sibling donor, we needed to flow enrich tumor cells from the “blast gate” to reduce contamination from the allograft donor, which would have confounded the sequencing results (Supplementary Methods). Whole genome, exome and transcriptome sequencing (RNA-seq) were performed using library construction and capture hybridization methods previously described [17, 18]. Alignment of whole genome and exome data was performed using the Genome Modeling System (GMS) essentially as described in Griffith et al [18].…”

“…Whole genome, exome and transcriptome sequencing (RNA-seq) were performed using library construction and capture hybridization methods previously described [17, 18]. Alignment of whole genome and exome data was performed using the Genome Modeling System (GMS) essentially as described in Griffith et al [18]. Germline and somatic variant detection was performed using multiple tools for each type of variant, including single nucleotide variants, small insertions and deletions, large amplifications and deletions, and structural variants.…”

Recurrent somatic mutations affecting B-cell receptor signaling pathway genes in follicular lymphoma

“…28 Briefly, paired-end reads were aligned to human reference sequence GRCh37, using BWA 29 (discovery) or BWA-MEM 30 (extension), and de-duplicated using Picard (http://broadinstitute.github.io/picard/). Variants were identified using SAMtools, 29 SomaticSniper, 31 VarScan, 32 MuTect, 33 Strelka, 34 Pindel, 35 and GATK, 36 and annotated using the GMS variant annotator (Ensembl v74).…”