Applying Ancestry and Sex Computation as a Quality Control Tool in Targeted Next-Generation Sequencing.

Objectives: To apply techniques for ancestry and sex computation from next-generation sequencing (NGS) data as an approach to confirm sample identity and detect sample processing errors.

Methods: We combined a principal component analysis method with k-nearest neighbors classification to compute the ancestry of patients undergoing NGS testing. By combining this calculation with X chromosome copy number data, we determined the sex and ancestry of patients for comparison with self-report.

Improving performance of multigene panels for genomic analysis of cancer predisposition.

Purpose: Screening multiple genes for inherited cancer predisposition expands opportunities for cancer prevention; however, reports of variants of uncertain significance (VUS) may limit clinical usefulness. We used an expert-driven approach, exploiting all available information, to evaluate multigene panels for inherited cancer predisposition in a clinical series that included multiple cancer types and complex family histories.

Methods: For 1,462 sequential patients referred for testing by BROCA or ColoSeq multigene panels, genomic DNA was sequenced and variants were interpreted by multiple experts using International Agency for Research on Cancer guidelines and incorporating evolutionary conservation, known and predicted variant consequences, and personal and family cancer history.

MSIplus for Integrated Colorectal Cancer Molecular Testing by Next-Generation Sequencing.

Molecular analysis of colon cancers currently requires multiphasic testing that uses various assays with different performance characteristics, adding cost and time to patient care. We have developed a single, next-generation sequencing assay to simultaneously evaluate colorectal cancers for mutations in relevant cancer genes (KRAS, NRAS, and BRAF) and for tumor microsatellite instability (MSI). In a sample set of 61 cases, the assay demonstrated overall sensitivity of 100% and specificity of 100% for identifying cancer-associated mutations, with a practical limit of detection at 2% mutant allele fraction.

Microsatellite instability detection by next generation sequencing.

Background: Microsatellite instability (MSI) is a useful phenotype in cancer diagnosis and prognosis. Nevertheless, methods to detect MSI status from next generation DNA sequencing (NGS) data are underdeveloped.

Methods: We developed an approach to detect the MSI phenotype using NGS (mSINGS).

Bioinformatics Resource Manager v2.3: an integrated software environment for systems biology with microRNA and cross-species analysis tools.

Background: MicroRNAs (miRNAs) are noncoding RNAs that direct post-transcriptional regulation of protein coding genes. Recent studies have shown miRNAs are important for controlling many biological processes, including nervous system development, and are highly conserved across species. Given their importance, computational tools are necessary for analysis, interpretation and integration of high-throughput (HTP) miRNA data in an increasing number of model species.