Maximizing Small Biopsy Patient Samples: Unified RNA-Seq Platform Assessment of over 120,000 Patient Biopsies.

Despite its wide-ranging benefits, whole-transcriptome or RNA exome profiling is challenging to implement in a clinical diagnostic setting. The Unified Assay is a comprehensive workflow wherein exome-enriched RNA-sequencing (RNA-Seq) assays are performed on clinical samples and analyzed by a series of advanced machine learning-based classifiers. Gene expression signatures and rare and/or novel genomic events, including fusions, mitochondrial variants, and loss of heterozygosity were assessed using RNA-Seq data generated from 120,313 clinical samples across three clinical indications (thyroid cancer, lung cancer, and interstitial lung disease).

Clinical validation and utility of Percepta GSC for the evaluation of lung cancer.

The Percepta Genomic Sequencing Classifier (GSC) was developed to up-classify as well as down-classify the risk of malignancy for lung lesions when bronchoscopy is non-diagnostic. We evaluated the performance of Percepta GSC in risk re-classification of indeterminate lung lesions. This multicenter study included individuals who currently or formerly smoked undergoing bronchoscopy for suspected lung cancer from the AEGIS I/ II cohorts and the Percepta Registry.

Characterization of universal features of partially methylated domains across tissues and species.

Background: Partially methylated domains (PMDs) are a hallmark of epigenomes in reproducible and specific biological contexts, including cancer cells, the placenta, and cultured cell lines. Existing methods for deciding whether PMDs exist in a sample, as well as their identification, are few, often tailored to specific biological questions, and require high coverage samples for accurate identification.

Results: In this study, we outline a set of axioms that take a step towards a functional definition for PMDs, describe an improved method for comparable PMD detection across samples with substantially differing sequencing depths, and refine the decision criteria for whether a sample contains PMDs using a data-driven approach.

Evolutionary expansion of DNA hypomethylation in the mammalian germline genome.

DNA methylation in the germline is among the most important factors influencing the evolution of mammalian genomes. Yet little is known about its evolutionary rate or the fraction of the methylome that has undergone change. We compared whole-genome, single-CpG DNA methylation profiles in sperm of seven species-human, chimpanzee, gorilla, rhesus macaque, mouse, rat, and dog-to investigate epigenomic evolution.

A reference methylome database and analysis pipeline to facilitate integrative and comparative epigenomics.

DNA methylation is implicated in a surprising diversity of regulatory, evolutionary processes and diseases in eukaryotes. The introduction of whole-genome bisulfite sequencing has enabled the study of DNA methylation at a single-base resolution, revealing many new aspects of DNA methylation and highlighting the usefulness of methylome data in understanding a variety of genomic phenomena. As the number of publicly available whole-genome bisulfite sequencing studies reaches into the hundreds, reliable and convenient tools for comparing and analyzing methylomes become increasingly important.

MLML: consistent simultaneous estimates of DNA methylation and hydroxymethylation.

Motivation: The two major epigenetic modifications of cytosines, 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC), coexist with each other in a range of mammalian cell populations. Increasing evidence points to important roles of 5-hmC in demethylation of 5-mC and epigenomic regulation in development. Recently developed experimental methods allow direct single-base profiling of either 5-hmC or 5-mC.