Biology subjects

Szydlowski, L.

Publications and source records attributed to Szydlowski, L..

3 recordsLinked to original sources

bioRxiv2024

Large protein databases reveal structural complementarity and functional locality

Recent breakthroughs in protein structure prediction have led to an unprecedented surge in high-quality 3D models, highlighting the need for efficient computational solutions to manage and analyze this wealth of structural data. In our work, we comprehensively examine the structural clusters obtained from the AlphaFold Protein Structure Database (AFDB), a high-quality subset of ESMAtlas, and the Microbiome Immunity Project (MIP). We create a single cohesive low-dimensional representation of the resulting protein space. Our results show that, while each database occupies distinct regions within the protein structure space, they collectively exhibit significant overlap in their functional profiles. High-level biological functions tend to cluster in particular regions, revealing a shared functional landscape despite the diverse sources of data. By creating a single, cohesive low-dimensional representation of protein structure space integrating data from diverse sources, localizing functional annotations within this space, and providing an open-access web-server for exploration, this work offers insights for future research concerning protein sequence-structure-function relationships, enabling various biological questions to be asked about taxonomic assignments, environmental factors, or functional specificity. This approach is generalizable to other or future datasets, enabling further discovery beyond findings presented here.

bioinformatics↗

bioRxiv2024

Expanding the cultivated human archaeome by targeted isolation of novel Methanobrevibacter strains from fecal samples

Archaea are integral components of the human microbiome but persist as understudied entities within the gastrointestinal tract (GIT), primarily due to the lack of cultured representatives for comprehensive mechanistic investigations. With only four Methanobrevibacter smithii isolates from humans available according to the Global Catalogue of Microorganisms (GCM), the existing cultures fail to adequately represent the observed diversity, as underscored by recent findings. This study introduces a targeted cultivation method for enriching methanogenic archaea from human fecal samples. Applied to 16 stool samples from healthy and diseased donors, the method aimed to genomically characterize the archaeal cultures and establish correlations with gastrointestinal disorders. The procedure combines methane breath testing, in silico metabolic modelling, media optimization, FACS, dilution series, and genomic sequencing through Nanopore technology. Additional analyses include co-cultured bacteriome, comparative genomics of archaeal genomes, functional comparisons, and structure-based protein function prediction of unknown differential traits. Successful establishment of stable archaeal cultures from 14 out of 16 fecal samples yielded nine previously uncultivated strains, eight of which were absent from a recent archaeome genome catalog. Comparative genomic and functional assessments of Methanobrevibacter smithii and Candidatus Methanobrevibacter intestini strains from diverse participant cohorts revealed features potentially associated with gastrointestinal diseases. This work substantially broadens the scope of available archaeal representatives for functional and mechanistic studies in the human GIT. The established protocol facilitates the cultivation of methanogenic archaea from nearly every human fecal sample, offering insights into the adaptability of Candidatus Methanobrevibacter intestini genomes in critical microbiome situations.

microbiology↗

bioRxiv2019

Evolutionary dynamics of microbial communities in bioelectrochemical systems.

Bio-electrochemical systems can generate electricity by virtue of mature microbial consortia that gradually and spontaneously optimize performance. To evaluate selective enrichment of these electrogenic microbial communities, five, 3-electrode reactors were inoculated with microbes derived from rice wash wastewater and incubated under a range of applied potentials. Reactors were sampled over a 12-week period and DNA extracted from anodal, cathodal, and planktonic bacterial communities was interrogated using a custom-made bioinformatics pipeline that combined 16S and metagenomic samples to monitor temporal changes in community composition. Some genera that constituted a minor proportion of the initial inoculum dominated within weeks following inoculation and correlated with applied potential. For instance, the abundance of Geobacter increased from 423-fold to 766-fold between -350 mV and -50 mV, respectively. Full metagenomic profiles of bacterial communities were obtained from reactors operating for 12 weeks. Functional analyses of metagenomes revealed metabolic changes between different species of the dominant genus, Geobacter, suggesting that optimal nutrient utilization at the lowest electrode potential is achieved via genome rearrangements and a strong inter-strain selection, as well as adjustment of the characteristic syntrophic relationships. These results reveal a certain degree of metabolic plasticity of electrochemically active bacteria and their communities in adaptation to adverse anodic and cathodic environments.

systems biology↗