Biology subjects

Son, K.

Publications and source records attributed to Son, K..

3 recordsLinked to original sources

bioRxiv2026

FateDriver: Weakly supervised dual-view graph learning for transition-specific prioritization of candidate regulators in cellular reprogramming

Cellular reprogramming supports regenerative medicine, yet the endogenous regulators of a specified source-to-target transition remain incompletely defined. Existing computational methods rank candidate regulators from network topology, trajectory dynamics, or cell-state labels, leaving unused the factors experimentally delivered to induce the transition. We present FateDriver, a weakly supervised dual-view graph neural network that jointly represents cells and genes from single-cell transcriptomes, treats the delivered factors as sparse gene-level labels, and ranks the remaining genes for a specified transition under a positive--unlabeled formulation. Across two OSKM datasets and one GMT dataset, FateDriver ranked first or second among six methods in recovering externally curated reference genes, exceeded a supervision-matched non-graph model despite weaker co-expression with the delivered factors, and achieved the highest recovery of protein targets of pluripotency-inducing chemical cocktails in both OSKM datasets. Holding either the source or the endpoint fixed yielded distinct candidate programs, including a DDX58--interferon axis associated with cells lacking endogenous pluripotency markers. Applying the same framework to candidate source--target pairs prioritized distinct candidate origins for two in vivo partially reprogrammed intestinal populations. FateDriver converts sparse experimental knowledge into transition-specific hypotheses for regulator prioritization from single-cell trajectories.

bioinformatics↗

bioRxiv2024

Sediment-associated processes drive spatial variation in ecosystem respiration in the Yakima River basin

Hyporheic zones (HZ) can contribute substantially to total stream ecosystem respiration (ERtot). HZ-focused process-based models may, therefore, effectively predict ERtot across sites, yet this remains untested under variable environmental conditions. Here we evaluate whether spatial variation in HZ respiration predicted via a process-based model explains spatial variation in field-estimates of ERtot across 33 sites in the Yakima River basin in Washington State, USA. We found that HZ respiration predictions did not explain spatial variation in field estimates of ERtot. To investigate further, we partitioned ERtot contributions into water column respiration (ERwc) and sediment-associated respiration (ERsed). ERsed contributed >50% of ERtot at 88% of sites, though relative contributions varied substantially. Despite this dominance, modeled HZ respiration explained neither spatial variation in ERtot nor in ERsed, suggesting that the HZ model alone does not capture the drivers of sediment-associated respiration across these sites. Instead, ERsed spatial variation was primarily explained by gross primary production, stream slope, velocity, and total dissolved nitrogen rather than median grain size, a primary control of HZ respiration predicted by the process-based model. Consistent with recent studies, our results indicate that improving basin-scale ERtot predictions requires integrating hydrologic and biogeochemical processes across hyporheic, benthic, and water column zones.

ecology↗

bioRxiv2023

Trabectedin derails transcription-coupled nucleotide excision repair to induce DNA breaks in highly transcribed genes

Most genotoxic anticancer agents fail in tumors with intact DNA repair. Therefore, trabectedin, a unique agent more toxic to cells with active DNA repair, specifically transcription-coupled nucleotide excision repair (TC-NER), provides new therapeutic opportunities. To unlock the potential of trabectedin and inform its application in precision oncology, a full mechanistic understanding of the drugs TC-NER-dependent toxicity is needed. Here, we determined that abortive TC-NER of trabectedin-DNA adducts forms persistent single-strand breaks (SSBs) as the adducts block the second of the two sequential NER incisions. We mapped the 3-hydroxyl groups of SSBs originating from the first NER incision at trabectedin lesions, recording TC-NER on a genome-wide scale. We showed that trabectedin-induced SSBs primarily occur in transcribed strands of active genes and peak near transcription start sites. Frequent SSBs were also found outside gene bodies, connecting TC-NER to divergent transcription from promoters. This work advances the use trabectedin for precision oncology and for studying TC-NER and transcription.

molecular biology↗