Biology subjects

Pham, C. M.

Publications and source records attributed to Pham, C. M..

3 recordsLinked to original sources

bioRxiv2026

OpusTaxa: A Unified Workflow for Taxonomic Profiling, Assembly, and Functional Analysis of Shotgun Metagenomes

Shotgun metagenomics has become a cornerstone of microbiome research, yet the complexity of existing workflows remains a major barrier for life scientists without dedicated bioinformatics support. Manual database setup, detailed sample sheet preparation, and management of software dependencies can make routine analysis difficult and time-consuming. Cross-study comparisons are further hampered by inconsistent processing pipelines, database versions, and profiling strategies, limiting reproducibility and the potential for large-scale meta-analyses. We present OpusTaxa, an open-source Snakemake workflow that provides end-to-end processing of short paired-end shotgun metagenomic data with minimal configuration. Users provide either FASTQ files or Sequence Read Archive accessions; OpusTaxa automatically downloads required databases, performs quality control, removes host reads, and executes taxonomic profiling, metagenome assembly, and functional analysis. All analysis modules can be independently toggled, and per-sample outputs are automatically merged into harmonised, cross-sample tables ready for downstream exploration. Across two public datasets, we demonstrate how OpusTaxa can be used to compare consistency across complementary taxonomic profilers and to estimate microbial load in addition to standard metagenomic workflows. AvailabilityOpusTaxa is freely available at https://github.com/yenkaiC/OpusTaxa. Documentation, test data, and example configurations are included in the repository.

bioinformatics↗

bioRxiv2025

Mitochondrial DNA Mutations Determine Favourable Molecular Responses to Targeted Kinase Inhibitor Therapy and Impair Oxidative Phosphorylation

Somatic mutations in mitochondrial DNA (mtDNA) are not typically considered key oncogenic drivers of cancer, primarily because of a high synonymous to non-synonymous variant ratio. Here, we surveyed 248 matched diagnosis and remission samples from patients with chronic myeloid leukemia (CML) and found a 75% had mitochondrial mutations with a median number of 2 mutations per patient. mtDNA mutations were predominantly non-synonymous, enriched in the D-loop control region, and likely originated from replication and transcriptional errors. Functionally, mtDNA mutations were associated with reduced oxidative phosphorylation (OXPHOS), as measured by Seahorse analyser. This metabolic vulnerability could be phenocopied by treatment with the complex I inhibitor IACS-10759 in combination with the targeted tyrosine kinase inhibitor (TKI) imatinib, which significantly reduced the colony-forming potential of TKI resistant leukemic stem/progenitor cells (LSPCs). Strikingly, we show that mtDNA mutations were associated with increased sensitivity to imatinib therapy in the clinic. Patients with [≥]3 mutations and patients with mutations in the D-loop showed significantly higher cumulative incidence of major molecular response at 24 months (90% vs. 68%, p = 0.004, and 89% vs 68%, p = 0.004 respectively). Single-cell RNA sequencing further revealed enrichment in non-synonymous mtDNA variants in LSPCs from TKI-sensitive patients, while TKI-resistant cells exhibited upregulated gene signatures related to glycerolipid and phospholipid metabolism and mitochondrial biogenesis. Together, our findings demonstrate that mtDNA mutations are key determinants of sensitivity to targeted therapy, rather than oncogenic drivers of leukemogenesis. Mechanistically, non-synonymous mtDNA mutations appear to restrict mitochondrial metabolic plasticity, with widespread implications for precision oncology.

cancer biology↗

bioRxiv2021

Adolescent rats extend help to outgroup members, highlighting a neural network for group identity categorization.

Prosocial behavior, in particular helping others in need, occurs preferentially in response to the perceived distress of ones own group members, or ingroup. The development of neural mechanisms underlying social selectivity towards ingroup members are not well established. Here, we used a rat helping behavior test to explore the development and neural basis of ingroup bias for prosocial behavior in adolescent rats. We previously found that adult rats selectively help others from their own social group, and that this selectivity is associated with activation in reward and motivation circuits. Surprisingly, we found that adolescent rats helped both ingroup and outgroup members, evidence suggesting that ingroup bias emerges in adulthood. Analysis of brain-wide neural activity, indexed by expression of the early-immediate gene c-Fos, revealed increased activity for ingroup members across a broad set of regions, which was congruent for adults and adolescents. However, adolescents showed reduced hippocampal and insular activity, and increased orbitofrontal cortex activity compared to adults. Adolescent rats who did not help trapped others also demonstrated increased amygdala connectivity. Together, these findings demonstrate that biases for group-dependent prosocial behavior develop with age in rats and suggest that specific brain regions contribute to this prosocial selectivity, overall pointing to possible targets for the functional modulation of ingroup bias. One Sentence SummaryProsocial selectivity increases with age in parallel with hippocampal and insular activation, providing insight into the neural classification of group membership.

neuroscience↗