Biology subjects

Ramanan, V.

Publications and source records attributed to Ramanan, V..

4 recordsLinked to original sources

bioRxiv2024

Sex differences in the clinical manifestation of autosomal dominant frontotemporal dementia

INTRODUCTIONSex differences are apparent in neurodegenerative diseases, but have not been comprehensively characterized in frontotemporal dementia (FTD). METHODSParticipants included 337 adults with autosomal dominant FTD enrolled in the ALLFTD Consortium. Clinical assessments and plasma were collected annually for up to six years. Linear mixed-effects models investigated how sex and disease stage associated with longitudinal trajectories of cognition, function, and neurofilament light chain (NfL). RESULTSWhile sex differences were not apparent at asymptomatic stages, females showed more rapid declines across all outcomes in symptomatic stages compared to males. In asymptomatic participants, the association between baseline NfL and clinical trajectories was weaker in females versus males, a difference that attenuated in symptomatic participants. DISCUSSIONIn genetic FTD, females show cognitive resilience in early disease stages followed by steeper clinical declines later in disease. Baseline NfL may be a less sensitive prognostic tool for clinical progression in females with FTD-causing mutations.

neuroscience↗

bioRxiv2024

Augmenting Bacterial Similarity Measures Using a Graph-Based Genome Representation

Relationships between bacterial taxa are traditionally defined using 16S rRNA nucleotide similarity or average nucleotide identity. Improvements in sequencing technology provides additional pairwise information on genome sequences, which may provide valuable information on genomic relationships. Mapping orthologous gene locations between genome pairs, known as synteny, is typically implemented in the discovery of new species and has not been systematically applied to bacterial genomes. Using a dataset of 378 bacterial genomes, we developed and tested a new measure of synteny similarity between a pair of genomes, which was scaled onto 16S rRNA distance using covariance matrices. Based on the input gene functions used (i.e., core, antibiotic resistance, and virulence), we observed varying topological arrangements of bacterial relationship networks by applying (1) complete linkage hierarchical clustering and (2) KNN graph structures to syntenic-scaled 16S data. Our metric improved clustering quality comparatively to state-of-the-art ANI metrics while preserving clustering assignments for the highest similarity relationships. Our findings indicate that syntenic relationships provide more granular and interpretable relationships for within-genera taxa compared to pairwise similarity measures, particularly in functional contexts. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/588602v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1bf81edorg.highwire.dtl.DTLVardef@1eaf18dorg.highwire.dtl.DTLVardef@198912dorg.highwire.dtl.DTLVardef@1633ee5_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL ABSTRACT.This method uses a novel measure based on shared synteny between bacterial genomes to scale 16S rRNA distance values. Created with BioRender.com. C_FIG

microbiology↗

bioRxiv2021

Diet and Domestication Drive Evolution of the Gut Holobiome

The host microbiome encompasses all microorganisms of a host. Host and microbiome coevolution in the gut result in differing microbial compositions, functionality, and host diet [1]. Host diet modulates what macromolecules are used for gut microbial metabolism, which can determine digestion, health, and behavior [2, 3]. Microbial composition across animals provides data on how microbiomes segregate between species and diets [4]. Here we show that microbiome data from GenBank can model host evolution, providing a "holobiome" insight to the important roles of diet and domestication. The main findings of this study in respect to microbial composition among species were: (1) herbivores are more similar than hosts with other diets; (2) domesticated species are more similar than wild relatives; and (3) humans are distinct from primates. Microbial composition between diets indicates a difference in functionality, where protein and fiber degradation are seen more in carnivores and herbivores respectively. Additionally, herbivores show the most microbial diversity among the diets. Finally, this analysis informs us of gaps in current microbiome data collection, which is biased toward pathogens. Thus, the host-microbiome relationship depicts a complex web of microbial functionality, composition, and diet that impact coevolution.

bioinformatics↗

bioRxiv2017

Interactions between species introduce spurious associations in microbiome studies

Microbiota contribute to many dimensions of host phenotype, including disease. To link specific microbes to specific phenotypes, microbiome-wide association studies compare microbial abundances between two groups of samples. Abundance differences, however, reflect not only direct associations with the phenotype, but also indirect effects due to microbial interactions. We found that microbial interactions could easily generate a large number of spurious associations that provide no mechanistic insight. Using techniques from statistical physics, we developed a method to remove indirect associations and applied it to the largest dataset on pediatric inflammatory bowel disease. Our method corrected the inflation of p-values in standard association tests and showed that only a small subset of associations is directly linked to the disease. Direct associations had a much higher accuracy in separating cases from controls and pointed to immunomodulation, butyrate production, and the brain-gut axis as important factors in the inflammatory bowel disease.

microbiology↗