Mark D. Fleming

IsoRanker uses long-read transcriptomics to prioritize non-coding variants in Mendelian conditions by detecting expression outliers, allelic imbalance, and NMD, leading to the identification of pathogenic variants in one individual.

The paper identifies POLDIP2 as a heme-sensing adaptor that facilitates CLPXP-mediated degradation of ALAS, elucidating the mechanism of heme-induced feedback regulation in heme biosynthesis.

The paper identifies mitochondrial DNA variants in undiagnosed rare disease families using exome and genome sequencing data, leading to diagnoses in 0.4% of cases.

The paper identifies differentially-localized protein isoforms generated by alternative start codon selection and shows their role in mitochondrial function, evolution, and disease.

This paper proposes a fetal actionable findings list for genomic sequencing in pregnancy to identify clinically relevant incidental variants.

The paper detects and classifies copy number variants in exome data from 6,633 families, identifying causal CNVs in 173 families and improving classification standards.

This study shows folate depletion induces erythroid differentiation by disrupting purine synthesis, with effects mimicked by SHIN1 inhibition and rescued by purine precursor supplementation.

The paper uses single-cell multi-omics to study how pathogenic mtDNA mutations are subject to purifying selection in immune cells from Pearson syndrome patients.

This study identifies DPP9 deficiency as a Mendelian disorder causing inflammasome hyperactivity, which can be rescued by reducing NLRP1/IL-1 signaling in mice.

The paper investigates how BOLA2 duplication in chromosome 16p11.2 affects iron homeostasis and anemia risk in autism patients, finding associations with anemia and iron deficiency.

The paper develops a method to detect mitochondrial heteroplasmy using NGS data and evaluates sources of mtDNA for clinical diagnostics.