Biology subjects

Cummings, B.

Publications and source records attributed to Cummings, B..

4 recordsLinked to original sources

bioRxiv2025

Phylogenomics supports monophyly of marsupial crustaceans: a journey to direct development

Peracarida (marsupial crustaceans) represent one of the most diverse and ecologically important crustacean groups, yet their evolutionary relationships have long been debated. Here, we present the most comprehensive phylogenomic analysis of Peracarida to date, incorporating the relict taxa Thermosbaenacea, Mictacea, Ingolfiellida, and Spelaeogriphacea for the first time in a phylogenomic framework. Our results robustly confirm peracarid monophyly and recover a well-supported clade uniting Mancoida (Isopoda, Tanaidaca, Cumacea), Mictacea, and Spelaeogriphacea. We propose the new taxon Panmancoida to encompass this expanded lineage defined by shared developmental and morphological traits. The inferred phylogeny further suggests that peracarid evolution involved a transition from an intermediate "pseudodirect" developmental mode to the direct development seen in most lineages. We further show that the shift to extensive brood care within the marsupium, accompanied by the loss of a free-swimming larval stage, may have accelerated rates of molecular evolution across lineages. Together, these findings provide a robust evolutionary framework for this major malacostracan lineage and highlight how key reproductive innovations reshaped the genomic and life-history trajectories of the marsupial crustaceans.

evolutionary biology↗

bioRxiv2021

Single-cell Chromatin Accessibility and Lipid Profiling Reveals a Metabolic Shift in Adipocytes Induced by Bariatric Surgery

Obesity promotes type 2 diabetes and cardiometabolic pathologies. Vertical sleeve gastrectomy (VSG) is used to treat obesity resulting in long-term weight loss and health improvements that precede weight loss; however, the mechanisms underlying the immediate benefits remain incompletely understood. Because adipose plays a crucial role in energy homeostasis and utilization, we hypothesized that VSG exerts its influences, in part, by modulating adipose functional states. We applied single-cell ATAC sequencing and lipid profiling to inguinal and epididymal adipose depots from mice that received sham surgery or VSG. We observed depot-specific cellular composition and chromatin accessibility patterns that were altered by VSG. Specifically, accessibility at Scd1, a fatty acid desaturase, was substantially reduced after VSG in mature adipocytes of inguinal but not epididymal depots. This was accompanied by reduced accumulation of SCD1-produced unsaturated fatty acids. Given these findings and reports that reductions in Scd1 attenuate obesity and insulin resistance and that unsaturated fatty acids stimulate glucose uptake, storage, and oxidation, our results suggest VSG exerts its beneficial effects through modifications of fatty acid profiles mediated by Scd1.

genomics↗

bioRxiv2021

Transcriptome variation in human tissues revealed by long-read sequencing

Regulation of transcript structure generates transcript diversity and plays an important role in human disease. The advent of long-read sequencing technologies offers the opportunity to study the role of genetic variation in transcript structure. In this paper, we present a large human long-read RNA-seq dataset using the Oxford Nanopore Technologies platform from 88 samples from GTEx tissues and cell lines, complementing the GTEx resource. We identified just under 100,000 new transcripts for annotated genes, and validated the protein expression of a similar proportion of novel and annotated transcripts. We developed a new computational package, LORALS, to analyze genetic effects of rare and common variants on the transcriptome via allele-specific analysis of long reads. We called allele-specific expression and transcript structure events, providing novel insights into the specific transcript alterations caused by common and rare genetic variants and highlighting the resolution gained from long-read data. We were able to perturb transcript structure upon knockdown of PTBP1, an RNA binding protein that mediates splicing, thereby finding genetic regulatory effects that are modified by the cellular environment. Finally, we use this dataset to enhance variant interpretation and study rare variants leading to aberrant splicing patterns.

genomics↗

bioRxiv2020

Compressive Big Data Analytics: An Ensemble Meta-Algorithm for High-dimensional Multisource Datasets

Health advances are contingent on continuous development of new methods and approaches to foster data driven discovery in the biomedical and clinical health sciences. Open-science offers hope for tackling some of the challenges associated with Big Data and team-based scientific discovery. Domain-independent reproducibility, area-specific replicability, curation, analysis, organization, management and sharing of health-related digital objects are critical components. This study expands the functionality and utility of an ensemble semi-supervised machine learning technique called Compressive Big Data Analytics (CBDA). Applied to high-dimensional data, CBDA identifies salient features and key biomarkers for reliable and reproducible forecasting of binary or multinomial outcomes. The method relies on iterative subsampling, combines function optimization and statistical inference, and generates ensemble predictions of observed univariate outcomes. In this manuscript, we extend the CBDA technique by (1) efficiently handling extremely large datasets, (2) generalizing the internal and external validation steps, (3) expanding the set of base-learners for joint ensemble prediction, (4) introduce an automated selection of CBDA specifications, and (5) provide mechanisms to assess CBDA convergence, evaluate the prediction accuracy, and measure result consistency. We validated the CBDA 2.0 technique using synthetic datasets as well as a population-wide census-like study, which grounds the mathematical models and the computational algorithm into translational health research settings. Specifically, we empirically validated the CBDA technique on a large-scale clinical study (UK Biobank), which includes imaging, cognitive, and clinical assessment data. The UK Biobank archive presents several difficult challenges related to the aggregation, harmonization, modeling, and interrogation of the information. These problems are related to the complex longitudinal structure, feature heterogeneity, multicollinearity, incongruency, and missingness, as well as violations of classical parametric assumptions that require novel health analytical approaches. Our results showcase the scalability, efficiency and potential of CBDA to compress complex data into structural information leading to derived knowledge and translational action. The results of the real case-study suggest new and exciting avenues of research in the context of identifying, tracking, and treating mental health and aging-related disorders. Following open-science principles, we share the entire end-to-end protocol, source-code, and results. This facilitates independent validation, result reproducibility, and team-based collaborative discovery.

bioinformatics↗