Retrospective identification of patients with SRRM2-related neurodevelopmental disorder in a single tertiary children's hospital.

SRRM2-related neurodevelopmental disorder is a recently described genetic diagnosis caused by loss-of-function variants in SRRM2. In order to understand the clinical spectrum of SRRM2-related neurodevelopmental disorder, we performed a retrospective exome data and clinical chart review at a single tertiary children's hospital, Children's Hospital of Philadelphia (CHOP). Among approximately 3100 clinical exome sequencing cases performed at CHOP, we identified three patients with SRRM2 loss-of-function pathogenic variants, in addition to one patient previously described in the literature.

Nuclear speckleopathies: developmental disorders caused by variants in genes encoding nuclear speckle proteins.

Nuclear speckles are small, membrane-less organelles that reside within the nucleus. Nuclear speckles serve as a regulatory hub coordinating complex RNA metabolism steps including gene transcription, pre-mRNA splicing, RNA modifications, and mRNA nuclear export. Reflecting the importance of proper nuclear speckle function in regulating normal human development, an increasing number of genetic disorders have been found to result from mutations in the genes encoding nuclear speckle proteins.

Synergy from gene expression and network mining (SynGeNet) method predicts synergistic drug combinations for diverse melanoma genomic subtypes.

Systems biology perspectives are crucial for understanding the pathophysiology of complex diseases, and therefore hold great promise for the discovery of novel treatment strategies. Drug combinations have been shown to improve durability and reduce resistance to available first-line therapies in a variety of cancers; however, traditional drug discovery approaches are prohibitively cost and labor-intensive to evaluate large-scale matrices of potential drug combinations. Computational methods are needed to efficiently model complex interactions of drug target pathways and identify mechanisms underlying drug combination synergy.