Biology subjects

Tomas, F.

Publications and source records attributed to Tomas, F..

5 recordsLinked to original sources

bioRxiv2024

TAD hierarchy restricts poised LTR activation and loss of TAD hierarchy promotes LTR co-option in cancer

Transposable elements (TEs) are abundant in the human genome, and they provide the sources for genetic and functional diversity. The regulation of TEs expression and their functional consequences in physiological conditions and cancer development remain to be fully elucidated. Previous studies suggested TEs are repressed by DNA methylation and chromatin modifications. The effect of 3D chromatin topology on TE regulation remains elusive. Here, by integrating transcriptome and 3D genome architecture studies, we showed that haploinsufficient loss of NIPBL selectively activates alternative promoters at the long terminal repeats (LTRs) of the TE subclasses. This activation occurs through the reorganization of topologically associating domain (TAD) hierarchical structures and recruitment of proximal enhancers. These observations indicate that TAD hierarchy restricts transcriptional activation of LTRs that already possess open chromatin features. In cancer, perturbation of the hierarchical chromatin topology can lead to co-option of LTRs as functional alternative promoters in a context-dependent manner and drive aberrant transcriptional activation of novel oncogenes and other divergent transcripts. These data uncovered a new layer of regulatory mechanism of TE expression beyond DNA and chromatin modification in human genome. They also posit the TAD hierarchy dysregulation as a novel mechanism for alternative promoter-mediated oncogene activation and transcriptional diversity in cancer, which may be exploited therapeutically.

cancer biology↗

bioRxiv2024

The Hitchhiker's Guide to Sequencing Data Types and Volumes for Population-Scale Pangenome Construction

Long-read (LR) technologies from Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) have transformed genomics research by providing diverse data types like HiFi, Duplex, and ultra-long ONT (ULONT). Despite recent strides in achieving haplotype-phased gapless genome assemblies using long-read technologies, concerns persist regarding the representation of genetic diversity, prompting the development of pangenome references. However, pangenome studies face challenges related to data types, volumes, and cost considerations for each assembled genome, while striving to maintain sensitivity. The absence of comprehensive guidance on optimal data selection exacerbates these challenges. To fill this gap, our study evaluates available data types, their significance, and the required volumes for robust de novo assembly in population-level pangenome projects. The results show that achieving chromosome-level haplotype-resolved assembly requires 20x high-quality long reads (HQLR) such as PacBio HiFi or ONT duplex, combined with 15-20x of ULONT per haplotype and 30x of long-range data such as Omni-C. High-quality long reads from both platforms yield assemblies with comparable contiguity, with HiFi excelling in NG50 and phasing accuracies, while usage of duplex generates more T2T contigs. As Long-Read Technologies advance, our study reevaluates recommended data types and volumes, providing practical guidelines for selecting sequencing platforms and coverage. These insights aim to be vital to the pangenome research community, contributing to their efforts and pushing genomic studies with broader impacts.

bioinformatics↗

bioRxiv2023

Int&in: a machine learning-based web server for split site identification in inteins

Inteins are proteins that excise themselves out of host proteins and ligate the flanking polypeptides in an auto-catalytic process called protein splicing. They are gaining momentum in synthetic biology for their ability to post-translationally modify proteins of interest. In nature, inteins are either contiguous or split, in which case the two intein fragments must first form a complex for the splicing to occur. So far, heuristic methods have been employed whenever a new split site in an intein had to be identified. To make the process of split site identification in inteins faster, easier and less costly, we developed Int&in, a web server that uses a gaussian Naive Bayes machine learning model to predict active and inactive split sites with high accuracy. The model was trained on a data set generated by us and validated using a large diverse data set from the literature, resulting in an accuracy of 0.76. Int&in will facilitate the engineering of novel split inteins for applications in biotechnology and synthetic biology.

synthetic biology↗

bioRxiv2023

Bite force transmission and mandible shape in grasshoppers, crickets, and allies is largely dependent on phylogeny, not diet

Although organ systems evolve in response to many intrinsic and extrinsic factors, frequently one factor has a dominating influence. For example, mouthpart shape and mechanics are thought to correlate strongly with aspects of the diet. Within insects, this paradigm of a shape-diet connection is advocated for decades but the relationship has so far never been quantified and is mostly based on qualitative observations. Orthoptera (grasshoppers, crickets, and allies) are a prominent case, for which mandible shape and dietary preference are thought to correlate strongly and even lead to predictions of feeding preferences. Here, we analysed mandible shape, biting efficiency, and their potential correlation with dietary categories in a phylogenetic framework for a broad sampling of several hundred extant Orthoptera covering nearly all families. The mandibular mechanical advantage was used as a descriptor of gnathal edge shape and bite force transmission efficiency. We aimed to understand how mandible shape is linked to biting efficiency and diet, and how these traits are influenced by phylogeny and allometry. The investigation reveals that feeding ecology is not the unequivocal predictor of mandible shape that it was assumed to be. There is a strong phylogenetic signal suggesting that phylogenetic history does have a much more prevalent influence on gnathal edge shape and distal mechanical advantage, than, e.g., feeding guilds or the efficiency of the force transmission to the food. Being ancestrally phytophagous, Orthoptera evolved in an environment with abundant food sources so that selective pressures leading to more specialized mouthpart shapes and force transmission efficiencies were low.

evolutionary biology↗

bioRxiv2020

Recovery and Community Succession of the Zostera marina Rhizobiome After Transplantation

Seagrasses can form mutualisms with their microbiomes that facilitate the exchange of energy sources, nutrients, and hormones, and ultimately impact plant stress resistance. Little is known about community succession within the belowground seagrass microbiome after disturbance and its potential role in the plants recovery after transplantation. We transplanted Zostera marina shoots with and without an intact rhizosphere and cultivated plants for four weeks while characterizing microbiome recovery and effects on plant traits. Rhizosphere and root microbiomes were compositionally distinct, likely representing discrete microbial niches. Furthermore, microbiomes of washed transplants were initially different from those of sod transplants, and recovered to resemble an undisturbed state within fourteen days. Conspicuously, changes in microbial communities of washed transplants corresponded with changes in rhizosphere sediment mass and root biomass, highlighting the strength and responsive nature of the relationship between plants, their microbiome, and the environment. Potential mutualistic microbes that were enriched over time include those that function in the cycling and turnover of sulfur, nitrogen, and plant-derived carbon in the rhizosphere environment. These findings highlight the importance and resiliency of the seagrass microbiome after disturbance. Consideration of the microbiome will have meaningful implications on habitat restoration practices. ImportanceSeagrasses are important coastal species that are declining globally, and transplantation can be used to combat these declines. However, the bacterial communities associated with seagrass rhizospheres and roots (the microbiome) are often disturbed or removed completely prior to transplantation. The seagrass microbiome benefits seagrasses through metabolite, nutrient, and phytohormone exchange, and contributes to the ecosystem services of seagrass meadows by cycling sulfur, nitrogen, and carbon. This experiment aimed to characterize the importance and resilience of the seagrass belowground microbiome by transplanting Zostera marina with and without intact rhizospheres and tracking microbiome and plant morphological recovery over four weeks. We found the seagrass microbiome to be resilient to transplantation disturbance, recovering after fourteen days. Additionally, microbiome recovery was linked with seagrass morphology, coinciding with increases in rhizosphere sediment mass and root biomass. Results of this study can be used to include microbiome responses in informing future restoration work.

microbiology↗