A user-driven machine learning approach for RNA-based sample discrimination and hierarchical classification.

RNA-based sample discrimination and classification can be used to provide biological insights and/or distinguish between clinical groups. However, finding informative differences between sample groups can be challenging due to the multidimensional and noisy nature of sequencing data. Here, we apply a machine learning approach for hierarchical discrimination and classification of samples with high-dimensional miRNA expression data.

Association of Histone H3 Trimethylation in Circulating Monocytes with Lack of Early Recurrence in Patients with Bladder Cancer following BCG Induction Therapy.

Background: The mode of action of Bacillus Calmette-Guérin (BCG) in the treatment of patients with non-muscle invasive bladder cancer (NMIBC) is incompletely understood, but recent studies support an association between BCG-induced trained immunity in circulating monocytes and disease-free survival.

Objective: We compared epigenetic profiles in monocytes from NMIBC patients with early disease recurrence with those from recurrence-free patients.

Methods: We conducted chromatin immunoprecipitation and DNA sequencing (ChIP-seq) on monocytes from seven patients treated with BCG (four with early recurrences and three recurrence-free after one year) to determine genome-wide distribution and abundance of histone 3 lysine 4 trimethylation (H3K4me3) prior to and after five weeks of induction therapy.

DNA polymerase ε and δ variants drive mutagenesis in polypurine tracts in human tumors.

Alterations in the exonuclease domain of DNA polymerase ε cause ultramutated cancers. These cancers accumulate AGA>ATA transversions; however, their genomic features beyond the trinucleotide motifs are obscure. We analyze the extended DNA context of ultramutation using whole-exome sequencing data from 524 endometrial and 395 colorectal tumors.

Establishing the role of the FES tyrosine kinase in the pathogenesis, pathophysiology, and severity of sepsis and its outcomes.

Introduction: Sepsis is a result of initial over-activation of the immune system in response to an infection or trauma that results in reduced blood flow and life-threatening end-organ damage, followed by suppression of the immune system that prevents proper clearance of the infection or trauma. Because of this, therapies that not only limit the activation of the immune system early on, but also improve blood flow to crucial organs and reactivate the immune system in late-stage sepsis, may be effective treatments. The tyrosine kinase FES may fulfill this role.