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Kodikara, S.

Publications and source records attributed to Kodikara, S..

9 recordsLinked to original sources

tensorOmics: Data integration for longitudinal omics data using tensor factorisation

Multi-omics studies capture comprehensive molecular profiles across biological layers to understand complex biological processes. A central challenge is integrating information across heterogeneous data types to identify coordinated molecular responses, particularly when measurements are collected longitudinally. Traditional integration methods can be broadly classified as unsupervised (exploring patterns without phenotypic information) or supervised (discriminating between groups or predicting outcomes). These approaches rely predominantly on matrix-based techniques that concatenate or project data into lower-dimensional spaces. However, matrix methods struggle with longitudinal data, as flattening multi-dimensional structures obscures temporal trajectories and violates independence assumptions. Tensor-based methods preserve the natural multi-way structure of longitudinal data but existing approaches are predominantly unsupervised, cannot incorporate phenotypic responses for discriminant analysis, and lack frameworks for integrating multiple omics layers. We present tensorOmics, a comprehensive framework for longitudinal omics analysis using tensor factorisation. The framework encompasses supervised and unsupervised methods for both single-omic (tensor PCA, tensor PLS discriminant analysis) and multi-omic settings (tensor PLS, block tensor PLS, block tensor PLS discriminant analysis). This unified approach captures coordinated responses across biological layers while preserving temporal structure. We validated tensorOmics through three case studies: antibiotic perturbation experiments, anaerobic digestion systems, and fecal microbiota transplantation. These applications demonstrate tensorOmics differentiates treatment groups, captures time-dependent molecular signatures, and reveals multi-layer coordinated responses that cross-sectional methods miss. Author summaryLongitudinal multi-omics studies track molecular changes over time to understand how biological systems respond to treatments, diseases, or environmental shifts. However, analysing these complex datasets presents significant challenges: traditional methods either flatten the time dimension, losing temporal information, or handle only single omics layers without integration. We developed tensorOmics, a comprehensive computational framework that preserves the natural three-way structure of longitudinal data (samples x features x time) while integrating multiple omics layers. Our approach combines tensor decomposition with multi-block analysis, offering five complementary methods that address both exploratory and supervised analyses across single and multi-omic settings. Through three diverse case studies (antibiotic recovery in humans, anaerobic digestion systems, and fecal microbiota transplantation), we demonstrate that tensorOmics successfully identifies biologically meaningful temporal signatures that distinguish treatment groups and reveal coordinated molecular responses across omic layers. The framework handles the unique statistical properties of different omics types and efficiently manages high-dimensional data through tensor-based data compression. tensorOmics is available as an R package, providing researchers with flexible tools to extract interpretable insights from longitudinal multi-omics experiments while properly accounting for repeated measurements and temporal dynamics.

bioinformatics↗

phylobar: an R package for multiresolution compositional barplots in omics studies

SummaryStacked barplots, though widely used in microbiome studies, can obscure important patterns in microbiome data. They omit rare taxa and can mask shifts that emerge at finer taxonomic levels. To address this issue, we introduce phylobar, an R package that interactively links stacked barplots with overview phylogenetic or taxonomic hierarchies. The interface allows users to collapse or expand subtrees, paint color palettes interactively, and search for specific taxa. This allows comparison across taxonomic resolutions that are hidden in static overviews. phylobar works with any omics data with hierarchical organization, including cell type hierarchies, as we demonstrate in a case study of immune cell composition in COVID-19 patients. Availability and Implementationphylobar is available as an R package on GitHub. It uses the htmlwidgets library to link interactive D3 visualizations with R. The interactive plots can be embedded within R Markdown or Quarto notebooks, and views can be exported as vector graphics files. The package is open source and documented at https://mkdiro-O.github.io/phylobar.

bioinformatics↗

Oral microbial signatures of head and neck cancer patients highlight diverse longitudinal patterns of oral mucositis severity

BackgroundOral mucositis is a painful complication commonly observed in head and neck cancer patients receiving cancer treatment. Emerging evidence suggests that changes in the oral microbiome can contribute to oral mucositis development, making microbial signatures potential targets for therapeutic inter-ventions. This study aimed to: (1) characterize longitudinal microbial patterns of oral mucositis severity among head and neck cancer patients; (2) determine clinically relevant patient clusters based on oral mucositis severity trajectories; and (3) identify microbial signatures specific to these clusters. ResultsWe derived a calibrated oral mucositis score by applying non-negative sparse principal component analysis to seven oral mucositis related symptom ratings, using longitudinal microbiome data from 140 head and neck cancer patients. Functional data analysis and hierarchical clustering identified three distinct patient clusters with differing microbial trajectories of oral mucositis progression. One cluster exhibited patients with a rapid increase in oral mucositis severity following treatment initiation, while the other clusters displayed more gradual increase. Demographic comparisons revealed significant differences in age and weight distributions between clusters, with older, lighter patients more common in clusters experiencing more gradual oral mucositis progression. Partial least squares knockoff analysis identified cluster-specific microbial signatures: notably, Prevotella spp. positively associated with calibrated oral mucositis score across all clusters, while Alloprevotella (Alloprevotella0302) was significantly enriched only in patients experiencing rapid oral mucositis progression. Conversely, genera associated with oral health, including Haemophilus, Rothia, and Actinomyces, were negatively correlated with calibrated oral mucositis score. ConclusionsDistinct trajectories of oral mucositis scores in head and neck cancer patients are linked to specific oral microbial profiles and demographic factors. The identification of cluster-specific microbial profiles highlights the potential for microbiome-targeted interventions to manage oral mucositis severity. While most taxa were cluster-specific, Prevotella consistently ranked among the top taxa positively associated with the calibirated oral mucositis score across clusters, suggesting it may not differentiate between patient groups but rather reflects overall disease severity.

bioinformatics↗

Multi-omics integration reveals sex-based differences in the circulating extracellular vesicle lipidome and miRNome of alcohol use disorder patients

Integrated multi-omics and extracellular vesicle (EV) analysis are emerging as powerful, complementary strategies for biomarker discovery. These approaches offer promising tools to enhance early detection, diagnosis, and treatment of alcohol use disorder (AUD). Here we applied an integrated miRNomic and lipidomic approach to analyze plasma EVs from AUD patients and controls of both sexes to gain a comprehensive understanding of the underlying molecular mechanisms. We identified an AUD signature with predictive potential for diagnostic applications. Individual features (e.g., hsa-miR-99b-3p, hsa-miR-556-5p, Cer_NDS-d39:1, and PI18:0_18:2) represented important components; however, the strength of this signature lay in the combined profile rather than isolated markers. We also revealed an AUD-sex signature that provided insight into how biological responses to alcohol differ between females and males (including features such as hsa-miR-1301-3p and PC39:4), which also underscored the power of multi-omic integration. The individual miRNome approach also revealed an opposite functional alteration by sex in various alcohol related systems, such as pathways associated with immunity, oxidative stress, and autophagy. An open-access Shiny web application (https://carpercle.shinyapps.io/SexEVEthOmics/) accompanies this study, providing interactive access to the complete dataset and additional analyses for customized exploration. Together, our findings underscore the added value of multi-omics integration in identifying clinically relevant molecular signatures of disease; this sex-informed approach offers a promising path toward more personalized diagnostic tools and therapeutic strategies in AUD.

bioinformatics↗

Impact of Molecular Crowding on Accessibility of Telomeric Overhangs Forming Multiple G-quadruplexes

Telomeric overhangs, composed of repeating GGGTTA sequences, can fold into multiple G-quadruplex (GQ) structures that are essential for maintaining genomic stability and regulating telomere length. Molecular crowding--a defining feature of the cellular environment--affects folding kinetics, conformation, and stability of individual GQs. However, its influence on the overall architecture and accessibility of telomeric overhangs containing multiple GQs remains largely unexplored. In this study, we employed single-molecule Forster Resonance Energy Transfer (smFRET) and FRET-Point Accumulation for Imaging in Nanoscale Topography (FRET-PAINT) to address this question. We examined the accessibility of telomeric overhangs capable of forming one to six GQs to a short complementary peptide nucleic acid (PNA) imager probe under molecular crowding conditions. These conditions were simulated by polyethylene glycol (PEG) molecules of two different molecular weights: 200 Da (PEG-200) and 6000 Da (PEG-6000). Our results reveal a systematic reduction in the overhang accessibility with increasing PEG concentration--showing approximately a 3-fold reduction at 30% (v/v) PEG-200 and an 8-fold reduction at 30% PEG-6000. We also observed a progressive compaction of the overhang as PEG concentration increased, suggesting molecular crowding promotes architectural condensation, thereby reducing probe accessibility. These findings offer new insights into how the crowded cellular environment may compact telomeric overhangs and modulate their structural and functional properties.

biophysics↗

Sequence-Dependent Liquid Crystalline Ordering of Gapped DNA

We investigate the impact of poly-adenine (poly-A) sequences on the type and stability of liquid crystalline (LC) phases formed by concentrated solutions of gapped DNA (two duplex arms bridged by a flexible single strand) using synchrotron small angle X-ray scattering and polarizing optical microscopy. While samples with mixed sequence form layered (smectic) phases, poly-A samples demonstrate a columnar phase at lower temperatures (5-35 {degrees}C), not previously observed in GDNA samples, and a smectic-B phase of exceptional stability at higher temperatures (35-65 {degrees}C). We present a model that connects formation of these LC phases with the unique characteristics of poly-A sequences, which manifest in various biological contexts, including DNA condensation and nucleosome formation.

biophysics↗

Semisynthetic Simulation for Microbiome Data Analysis

High-throughput sequencing data lie at the heart of modern microbiome research. Effective analysis of these data requires careful preprocessing, modeling, and interpretation to detect subtle signals and avoid spurious associations. In this review, we discuss how simulation can serve as a sandbox to test candidate approaches, creating a setting that mimics real data while providing ground truth. This is particularly valuable for power analysis, methods benchmarking, and reliability analysis. We explain the probability, multivariate analysis, and regression concepts behind modern simulators and how different implementations make trade-offs between generality, faithfulness, and controllability. Recognizing that all simulators only approximate reality, we review methods to evaluate how accurately they reflect key properties. We also present case studies demonstrating the value of simulation in differential abundance testing, dimensionality reduction, network analysis, and data integration. Code for these examples is available in an online tutorial (https://go.wisc.edu/8994yz) that can be easily adapted to new problem settings.

bioinformatics↗

Protection of the Telomeric Junction by the Shelterin Complex

Shelterin serves critical roles in suppressing superfluous DNA damage repair pathways on telomeres. The junction between double-stranded telomeric tracts (dsTEL) and single-stranded telomeric overhang (ssTEL) is the most accessible region of the telomeric DNA. The shelterin complex contains dsTEL and ssTEL binding proteins and can protect this junction by bridging between the ssTEL and dsTEL tracts. To test this possibility, we monitored shelterin binding to telomeric DNA substrates with varying ssTEL and dsTEL lengths and quantified its impact on telomere accessibility using single-molecule fluorescence microscopy methods in vitro. We identified the first dsTEL repeat nearest to the junction as the preferred binding site for creating the shelterin bridge. Shelterin requires at least two ssTEL repeats while the POT1 subunit of shelterin that binds to ssTEL requires longer ssTEL tracts for stable binding to telomeres and effective protection of the junction region. The ability of POT1 to protect the junction is significantly enhanced by the 5-phosphate at the junction. Collectively, our results show that shelterin enhances the binding stability of POT1 to ssTEL and provides more effective protection compared to POT1 alone by bridging single- and double-stranded telomeric tracts. Table of Content Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/608453v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@a58e79org.highwire.dtl.DTLVardef@12cb172org.highwire.dtl.DTLVardef@135bf40org.highwire.dtl.DTLVardef@19f3fe4_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

Microbial network inference for longitudinal microbiome studies with LUPINE

The microbiome is a complex ecosystem of interdependent taxa that has traditionally been studied through cross-sectional studies. However, longitudinal microbiome studies are becoming increasingly popular. These studies enable researchers to infer taxa associations towards the understanding of coexistence, competition, and collaboration between microbes across time. Traditional metrics for association analysis, such as correlation, are limited due to the data characteristics of microbiome data (sparse, compositional, multivariate). Several network inference methods have been proposed, but have been largely unexplored in a longitudinal setting. We introduce LUPINE (LongitUdinal modelling with Partial least squares regression for NEtwork inference), a novel approach that leverages on conditional independence and low-dimensional data representation. This method is specifically designed to handle scenarios with small sample sizes and small number of time points. LUPINE is the first method of its kind to infer microbial networks across time, while considering information from all past time points and is thus able to capture dynamic microbial interactions that evolve over time. We validate LUPINE and its variant, LUPINE single (for single time point analysis) in simulated data and four case studies, where we highlight LUPINEs ability to identify relevant taxa in each study context, across different experimental designs (mouse and human studies, with or without interventions, as short or long time courses). We propose different metrics to compare the inferred networks and detect changes in the networks across time, groups or in response to external disturbances. LUPINE is a simple yet innovative network inference methodology that is suitable for, but not limited to, analysing longitudinal microbiome data. The R code and data are publicly available for readers interested in applying these new methods to their studies.

bioinformatics↗