Biology subjects

Fosso, B.

Publications and source records attributed to Fosso, B..

6 recordsLinked to original sources

bioRxiv2026

FAIRyMAGs - a series of FAIR Galaxy workflows for the generation of metagenome assembled genomes

Advances in whole-genome sequencing (WGS) technologies have enabled large-scale recovery of metagenome-assembled genomes (MAGs), providing unprecedented insights into microbial diversity across diverse environments. However, the reconstruction of MAGs remains computationally demanding and methodologically complex, requiring the integration of multiple tools for quality control, assembly, binning, refinement, and annotation. Existing workflows often rely on scripting-based implementations, constrain user-driven modification and stepwise execution, and require advanced expertise in high-performance computing (HPC) system administration, thereby limiting accessibility, reproducibility, and adaptability. Here, we present FAIRyMAGs, a Findable, Accessible, Interoperable, and Reusable (FAIR)-compliant, modular pipeline implemented within the Galaxy platform for the generation and analysis of MAGs. FAIRyMAGs consists of six interconnected workflows covering all major steps of MAG reconstruction, including read preprocessing, host and contaminant removal, assembly, binning, dereplication, and downstream taxonomic and functional annotation. The workflows are accompanied by extensive training material, including tutorials, a learning pathway, FAQs, test datasets and video walk-throughs by domain experts, supporting community adaptation. By leveraging Galaxys graphical interface and federated infrastructure, FAIRyMAGs enables users to execute complex analyses on public or private compute resources without requiring local installation or workflow programming expertise. The modular design further supports flexible adaptation, iterative optimization, and seamless integration of new tools contributed by the community. To demonstrate applicability, FAIRyMAGs was applied to four real-world microbiome datasets spanning various host-associated and environmental systems. These analyses revealed substantial variability in MAG recovery, community complexity, and clustering structure, underscoring the importance of flexible workflows adaptable to dataset-specific characteristics. Overall, FAIRyMAGs provides an accessible, extensible, and reproducible framework for genome-resolved metagenomics, reducing technical barriers and enabling methodological innovation through community-driven development within the adaptable Galaxy ecosystem.

bioinformatics↗

bioRxiv2026

Stage-dependent chromatin accessibility remodeling defines an architectural state in facioscapulohumeral muscular dystrophy myoblasts

Facioscapulohumeral muscular dystrophy (FSHD) has been linked to alterations in higher-order genome organization, yet how these structural perturbations shape chromatin accessibility across muscle developmental stages remains unclear. Here, we identify a stage-specific architectural chromatin accessibility state that defines proliferating FSHD myoblasts. Using genome-wide ATAC-seq profiling of primary human myoblasts and differentiated myotubes, analyzed using the telomere-to-telomere (T2T-CHM13) human reference genome, we map the genome-wide distribution and hierarchical organization of this state. We detect extensive chromatin accessibility remodeling, with over 12,000 differentially accessible regions in myoblasts and marked attenuation of this state upon terminal differentiation. Remodeling predominantly affects intronic and distal intergenic regions enriched in non-coding and repeat-proximal sequences, indicating redistribution of regulatory accessibility beyond promoter-centered regulation. At the chromosome scale, accessibility losses cluster within megabase domains enriched in heterochromatin- and nucleolus-associated regions, revealing coordinated reorganization of nuclear architecture. No reproducible accessibility changes occur within the D4Z4 repeat array or canonical DUX4 target loci, demonstrating that early architectural remodeling in FSHD myoblasts is largely uncoupled from sustained DUX4-driven programs. These findings these findings define a transient architectural chromatin accessibility state that emerges in proliferating FSHD myoblasts and is largely resolved upon terminal differentiation. Our work supports a model in which disruption of higher-order genome organization represents an early and stage-restricted determinant of disease susceptibility.

genomics↗

bioRxiv2024

Environmentally-mediated selection parallels population divergence across a chimpanzee subspecies contact zone

Species evolve from populations with ancestor-descendant relationships in a bifurcating process shaped by geography, gene flow, genetic drift, and natural selection leading to local adaptation to prevailing environmental and ecological conditions. Building on this foundational understanding, we explored local adaptation in chimpanzees (Pan troglodytes) at a key geographical intersection in Cameroon where the two main chimpanzee phylogenetic lineages converge. The Nigeria-Cameroon chimpanzee (P. t. ellioti) and central chimpanzee (P. t. troglodytes) last shared a common ancestor about 500 thousand years ago, with occasional gene flow between them. The evolutionary processes driving their prolonged separation are not fully understood, but neutral evolutionary mechanisms alone cannot account for the observed divergence pattern. Cameroon is often referred to as Africa in miniature because the Gulf of Guinea Forest, Congo Basin Forest, and savanna converge there, forming an ecotone. Thus, this contact zone between subspecies in Cameroon provides a unique natural laboratory that enabled us to investigate how environmental variation and natural selection shape divergence in chimpanzees. We developed a genome-wide panel of single-nucleotide polymorphisms (SNPs) in 112 wild chimpanzees sampled in multiple habitats across this contact zone. We augmented SNP discovery by sequencing eight new chimpanzee genomes from Cameroon and analyzing them with previously published chimpanzee genomes. We found that P. t. ellioti and P. t. troglodytes diverged from one another around 478,000 years ago and occasionally exchange migrants. We identified 1,690 unique SNPs across 905 genes associated with 31 environmental variables that describe the habitat. These genes are involved in essential biological processes, including immune response, neurological development, behavior, and dietary adaptations. This study highlights the importance of understanding the geographical context of natural selection, paving the way for future studies to interpret evidence for genetic variation with phenotypic traits and deepening our understanding of how populations diverge in response to environmental pressures. Author SummaryWe investigated how local adaptation contributes to shaping the diversification of chimpanzee subspecies at the geographical convergence point for the two major branches of the chimpanzee phylogenetic tree. We analyzed genome-wide SNP genotypes of 112 chimpanzees sampled from natural communities located in this understudied area. We used tiered methods that identified 905 genes subject to selection, each associated with one or more of 31 environmental predictors describing the habitat. We found strong signals of selection in immune response genes that separate P. t. troglodytes from P. t. ellioti, highlighting the important role of different pathogen histories in their evolution. We also found evidence of selection in genes associated with neurological development, behavior, and diet, that separate both the subspecies and populations of P. t. ellioti that occupy different niches. These findings suggest that ecological and cultural factors may also contribute to shaping the diversification of chimpanzees across the contact zone.

genomics↗

bioRxiv2024

A novel family of lncRNAs relate facioscapulohumeral muscular dystrophy to nucleolar architecture and protein synthesis rate

Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary myopathy linked to deletions of the tandemly arrayed D4Z4 macrosatellite repeats at human chromosome 4q35. These deletions accompany local chromatin changes and the anomalous expression of nearby transcripts FRG2A, DBET, and D4Z4. We discovered that FRG2A is one member of a family of long non-coding RNAs (lncRNAs) expressed at elevated levels in skeletal muscle cells with distinct amounts detected in individual patients. We found that FRG2A lncRNA preferentially associates with rDNA sequences and centromeres and promotes the three-dimensional association of centromeres with the nucleolar periphery in FSHD cells. Furthermore, we demonstrate that the elevated FRG2A expression in cells from FSHD patients reduces rDNA transcription and global protein synthesis. Our results frame an entirely unanticipated new disease model in which elevated lncRNAs levels mediated by deletions of D4Z4 macrosatellite repeats leads to a diminished protein synthesis capacity, thereby contributing to muscle wasting.

molecular biology↗

bioRxiv2021

Natural and after colon washing fecal samples: the two sides of the coin for investigating the human gut microbiome

To date there are several studies focusing on the importance of gut microbiome for human health, however the selection of a universal sampling matrix representative of the microbial biodiversity associated to the gastrointestinal (GI) tract, still represents a challenge. Here we present a study in which, through a deep metabarcoding analysis of the 16S rRNA gene, we compared two sampling matrices, feces (F) and colonic lavage liquid (LL), in order to evaluate their accuracy to represent the complexity of the human gut microbiome. A training set of 37 volunteers was attained and paired F and LL samples were collected from each subject. A preliminary absolute quantification of total 16S rDNA, performed by droplet digital PCR (ddPCR), confirmed that sequencing and taxonomic analysis were performed on same total bacterial abundance obtained from the two sampling methods. The taxonomic analysis of paired samples revealed that, although specific taxa were predominantly or exclusively observed in LL samples, as well as other taxa were detectable only or were predominant in stool, the microbiomes of the paired samples F and LL in the same subject hold overlapping taxonomic composition. Moreover, LL samples revealed a higher biodiversity than stool at all taxonomic ranks, as demonstrated by the Shannon Index and the Inverse Simpsons Index. We also found greater inter-individual variability than intra-individual variability in both sample matrices. Finally, functional differences were unveiled in the gut microbiome detected in the F and LL samples. A significant overrepresentation of 22 and 13 metabolic pathways, mainly occurring in Firmicutes and Proteobacteria, was observed in gut microbiota detected in feces and LL samples, respectively. This suggests that LL samples may allow for the detection of microbes adhering to the intestinal mucosal surface as members of the resident flora that are not easily detectable in stool, most likely representative of a diet-influenced transient microbiota. This first comparative study on feces and LL samples for the study of the human gut microbiome demonstrates that the use of both types of sample matrices may represent a possible choice to obtain a more complete view of the human gut microbiota in response to different biological and clinical questions.

molecular biology↗

bioRxiv2021

Loss of C3aR induces immune infiltration and inflammatory microbiota in a novel spontaneous model of colon cancer

Several lines of evidence suggest that inflammation plays a pivotal role in the development and progression of colorectal cancer (CRC) and can be unleashed by the loss of innate immunosurveillance. The complement system is a well characterized first line of defense against pathogens and a central component of the immune response. Emerging evidence suggests that complement anaphylatoxin C3a produced upon complement activation and acting via its receptor (C3aR) may play a role in intestinal homeostasis. However, to date, it is unknown whether and how the C3a/C3aR axis can affect CRC. By mining publicly available datasets, we found that CpG island methylation of c3ar1 occurs in CRC patients and is associated with significant downregulation of C3aR. By reverse-translating this finding we were able to shift in APCMin/+ mice the tumorigenesis from the small intestine to the colon therefore generating a novel mouse model, which more closely mirrors the CRC in humans. Transcriptomic analysis on colorectal polyps from our newly developed genetic mouse model revealed a significant increase in innate and adaptive immune signatures in absence of C3aR. Furthermore, loss of C3aR significantly impacted the fecal and tumor-associated microbiota and supported the blooming of pro-inflammatory bacterial species as confirmed by experiments of fecal microbiota transplantation. Future studies will elucidate whether loss of C3aR can be exploited as a biomarker for sub-groups of CRC and whether the C3a/C3aR axis may be exploited for the generation of more effective therapeutic interventions.

immunology↗