Vladimir B. Seplyarskiy

This study shows that extrachromosomal circular DNA (eccDNA) in the male germline can integrate into the genome and contribute to structural variations, with diabetes increasing eccDNA levels in sperm.

The paper estimates mutation rates and variant effects using 700k exomes to identify genes with mutational hotspots and improve variant prioritization for genetic diagnostics.

gnomAD v4 (730,947 exomes) brings LOFTEE-2 loss-of-function annotation (0.90 precision, strict mode), missense-aware constraint, and LLM-mined literature evidence combined with constraint to rank disease genes.

The paper identifies a hypermutation hotspot at transcription start sites in the human germline, linked to early embryogenesis and distinct from known mutagenic processes.

The paper identifies genes with hypermutable de novo mutations as potential drivers of clonal expansions in spermatogonia, highlighting their impact on mutation rates and disease associations.

The paper uses DNA lesion segregation to estimate tumor initiating events and shows early cancer drivers have a fitness advantage exceeding 30%.

This study develops a phylogeny-based method to identify mutational processes in primates, revealing nine distinct processes with seven having underlying biological mechanisms.

The paper introduces SigNet, a deep learning method for mutational signature decomposition, showing improved accuracy and robustness in estimating signature contributions in cancer genomes.

The paper introduces a basepair-resolution mutation rate model, Roulette, which identifies a 10-fold increase in mutation rate for Polymerase III-transcribed genes and detects elevated rates in testis-specific transcription factor binding sites.

The paper investigates the effect of an inherited POLD1 variant on mutation rates in germline and somatic cells, showing a recessive effect on proofreading deficiency in cancer.

The paper identifies prenatal mutational processes in schizophrenia brains linked to transcription factor binding sites and proposes a new term 'skiagenesis' for these mutations.

The paper decomposes mutation rate and spectra variation in human germline using blind source separation, identifying nine processes including those related to DNA damage and replication timing.

The paper identifies maternal age-related mutation clusters in germline de novo mutations linked to double-strand break processes.

The paper shows POLD1 replicates both strands within 1 kb of replication origins, with mutational bias indicating most origins fire and only a quarter result in processive forks.

The paper shows APOBEC3A/B causes 20% of heritable C→T and C→G mutations in humans, preferentially on the lagging strand.