Biology subjects

Baum, S.

Publications and source records attributed to Baum, S..

5 recordsLinked to original sources

bioRxiv2026

MAAMOUL: Metabolic network-based discovery of microbiome-metabolome shifts in disease

MotivationA central goal in human gut microbiome research is to identify disease-associated functional shifts, an objective increasingly pursued through metagenomic and metabolomic assays. However, common differential abundance analyses of genes or metabolites often yield long and difficult-to-interpret feature lists. Aggregating features into predefined pathways can improve interpretability but relies on fixed pathway boundaries that may not reflect context-specific functional changes. Moreover, even when paired metagenomic-metabolomic data are available, they are often analyzed separately or linked only through simple statistical associations. ResultsWe introduce MAAMOUL, a knowledge-based computational framework that integrates metagenomic and metabolomic data to identify disease-associated, data-driven microbial metabolic modules. Leveraging prior knowledge of bacterial metabolism, MAAMOUL maps disease-association scores onto a global microbiome-wide metabolic network and identifies custom modules enriched for altered genes and metabolites. Applying MAAMOUL to inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) datasets revealed significant disease-associated modules not detected by conventional pathway-level analysis. In IBD, modules reflected disrupted sulfur and aromatic amino acid metabolism and enhanced microbial nucleotide salvage, whereas in IBS they linked purine and nicotinate/nicotinamide metabolism. These results demonstrate that network-guided multi-omic integration can uncover coherent functional shifts in the gut microbiome overlooked by single-omic or purely statistical approaches. AvailabilityMAAMOUL is available as an R package at https://github.com/borenstein-lab/MAAMOUL.

bioinformatics↗

bioRxiv2025

TAGINE: Fast Taxonomy-based Feature Engineering for Microbiome Analysis

SummaryTAGINE is a feature engineering algorithm that leverages the microbial taxonomic tree to optimize feature sets in microbiome data for predictive modeling. The algorithm starts with features at high taxonomic levels and iteratively splits them into lower-level clades in cases where it improves predictive accuracy, ultimately producing a feature set spanning multiple taxonomic levels. This approach aims to markedly reduce the number of features while preserving biological relevance and interpretability. We compare TAGINEs performances to other standard and taxonomy-based feature engineering methods on several different datasets, and show that TAGINE yields more compact feature sets and is orders of magnitude faster than other methods, while maintaining predictive accuracy. Availability and ImplementationTAGINE is freely available under the MIT license with source code available at https://github.com/borenstein-lab/tagine_fe.

bioinformatics↗

bioRxiv2024

Repetition of Rhythmic Patterns Fosters Neural Representation of Musical Meter

Music often entails perception of periodic pulses (hereafter meter) which serve as an internal temporal reference to coordinate movements to music. Crucially, meter perception arises even when the musical rhythm only weakly cues meter periodicities (i.e., syncopated rhythms). However, syncopated rhythms are often looped in music, suggesting that repetition of rhythmic patterns may facilitate meter perception by providing periodic cues at a slower, supra-second timescale. Here, we tested this hypothesis by recording separately electroencephalographic (EEG) and behavioral responses (finger tapping) while participants listened to different syncopated rhythmic sequences. These sequences either consisted of a repeated pattern (repetition of 4.8 and 9.6-s patterns) or were generated without repetition. EEG responses showed overall periodization of the rhythmic input, at periodicities corresponding to those expressed as the meter in behavioral responses, and in contrast with the weak cues to these periodicities in the rhythmic inputs. Most importantly, pattern repetition strengthened this neural representation of the meter, demonstrating that supra-second periodicities in the rhythmic input further enhance sub-second periodicities in neural activity. These findings thus highlight the multiscale nature of temporal processes at stake in processing musical rhythm, and, more generally, complex rhythmic inputs involved in interpersonal interaction and communication.

neuroscience↗

bioRxiv2024

Protein catabolites as blood-based biomarkers of aging physiology: Findings from the Dog Aging Project

Our understanding of age-related physiology and metabolism has grown through the study of systems biology, including transcriptomics, single-cell analysis, proteomics and metabolomics. Studies in lab organisms in controlled environments, while powerful and complex, fall short of capturing the breadth of genetic and environmental variation in nature. Thus, there is now a major effort in geroscience to identify aging biomarkers and to develop aging interventions that might be applied across the diversity of humans and other free-living species. To meet this challenge, the Dog Aging Project (DAP) is designed to identify cross-sectional and longitudinal patterns of aging in complex systems, and how these are shaped by the diversity of genetic and environmental variation among companion dogs. Here we surveyed the plasma metabolome from the first year of sampling of the Precision Cohort of the DAP. By incorporating extensive metadata and whole genome sequencing information, we were able to overcome the limitations inherent in breed-based estimates of genetic and physiological effects, and to probe the physiological and dietary basis of the age-related metabolome. We identified a significant effect of age on approximately 40% of measured metabolites. Among other insights, we discovered a potentially novel biomarker of age in the post-translationally modified amino acids (ptmAAs). The ptmAAs, which can only be generated by protein hydrolysis, covaried both with age and with other biomarkers of amino acid metabolism, and in a way that was robust to diet. Clinical measures of kidney function mediated about half of the higher ptmAA levels in older dogs. This work identifies ptmAAs as robust indicators of age in dogs, and points to kidney function as a physiological mediator of age-associated variation in the plasma metabolome.

systems biology↗

bioRxiv2021

Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice

The loss of skeletal muscle function with age, known as sarcopenia, significantly reduces independence and quality of life and can have significant metabolic consequences. Although exercise is effective in treating sarcopenia it is not always a viable option clinically, and currently there are no pharmacological therapeutic interventions for sarcopenia. Here we show that chronic treatment with pan-adiponectin receptor agonist AdipoRon improved muscle function in male mice by a mechanism linked to skeletal muscle metabolism and tissue remodeling. In aged mice, 6 weeks of AdipoRon treatment improved skeletal muscle functional measures in vivo and ex vivo. Improvements were linked to changes in fiber type, including an enrichment of oxidative fibers, and an increase in mitochondrial activity. In young mice, 6 weeks of AdipoRon treatment improved contractile force and activated the energy sensing kinase AMPK and the mitochondrial regulator PGC-1a (peroxisome proliferator activated receptor gamma coactivator 1 alpha). In cultured cells, the AdipoRon induced stimulation of AMPK and PGC-1a was associated with increased mitochondrial membrane potential, reorganization of mitochondrial architecture, increased respiration, and increased ATP production. Furthermore, the ability of AdipoRon to stimulate AMPK and PGC1a was conserved in nonhuman primate cultured cells. These data show that AdipoRon is an effective agent for the prevention of sarcopenia in mice and indicate that its effects translate to primates, suggesting it may also be a suitable therapeutic for sarcopenia in clinical application.

physiology↗