Biology subjects

Seckin, E.

Publications and source records attributed to Seckin, E..

4 recordsLinked to original sources

bioRxiv2026

Evaluating transformer-based models for structural characterization of orphan proteins

MotivationTransformer-based models (TBMs) are state-of-the-art deep learning architectures that predict protein structural features with high accuracy. Despite methodological differences, they all rely on large protein sequence datasets structured by homology, as homologous proteins typically share similar structures. However, 5-30% of eukaryotic proteomes consist of orphan proteins--sequences without detectable similarity to known families. Although they may share structural traits with characterized proteins, their lack of homology makes them and ideal dataset for evaluating TBM generalization beyond familiar sequence space. ResultsWe compared predictions from several widely used TBM architectures on an expert-curated set of orphan proteins from the Meloidogyne genus. None of these proteins has an experimentally determined structure. To assess model performance, we conducted consistency analyses, comparing predicted features with those observed in sets of known homologous proteins and across models. Multiple sequence alignment-based approaches such as AlphaFold2 performed poorly on orphan proteins, as did single-sequence or embedding-based language models including ESMFold, OmegaFold, and ProtT5. This limited performance cannot be fully attributed to intrinsic disorder, as confirmed by independent non-TBM disorder predictors. While accurate tertiary structure prediction remains out of reach, secondary structure is more reliably captured: predictors share about 70% of secondary structure elements on average, regardless of global fold similarity, and these elements are consistently identified by dedicated secondary structure tools. AvailabilityAll data and analysis scripts are available at https://doi.org/10.5281/zenodo.18788931 Contactedoardo.sarti@inria.fr

bioinformatics↗

bioRxiv2026

Plant-parasitic nematode microRNAs hijack plant AGO1 to induce host-cell reprogramming

Cross-kingdom RNA interference (ckRNAi) is emerging as a mode of inter-organismal gene regulation, yet mechanistic examples in plant-metazoan interactions remain limited. Here, we demonstrate miRNA-driven ckRNAi in the nematode-plant pathosystem. Root-knot nematodes are among the most destructive plant pathogens, reprogramming root tissues to develop into galls containing multinucleated, hypermetabolic giant feeding cells essential for parasitism. AGO1-associated small-RNA immunoprecipitation (AGO1-RIP) from tomato galls revealed the selective in planta loading of 10 M. incognita miRNAs into host AGO1. Integrating degradome profiling, target prediction, and dual-luciferase reporter assays, we validated miRNA-directed silencing of nine tomato transcripts by four secreted nematode miRNAs. These targets map to major pathway classes involved in immune signaling, metabolic regulation, and cellular reprogramming linked to feeding-site establishment. Functional analyses further show that the nematode-secreted miR-2b is enhances giant feeding cell development. Comparative AGO1-RIP in Arabidopsis thaliana identified a conserved subset of AGO1-loaded nematode miRNAs, including miR-2b and miR-100, consistent with shared small-RNA effectors across hosts. Finally, the overlap between AGO1-loaded miRNA families and helminth secreted small-RNA repertoires supports evolutionary convergence on RNA-based virulence strategies. Collectively, our findings establish miRNA-mediated ckRNAi as a mechanistic component of plant-root-knot nematode interactions and provide a framework for leveraging RNA-based vulnerabilities for nematode control.

plant biology↗

bioRxiv2025

Identification, evolutionary history and characteristics of orphan genes in root-knot nematodes

Orphan genes, lacking detectable homologs in other species, are common across eukaryotic genomes and can arise through divergence of existing genes or de novo from non-coding regions. Here we identified and characterized orphan genes in eight root-knot nematode species (genus Meloidogyne), the most destructive plant-parasitic nematodes. For that, we used comparative genomics across 85 nematodes, ancestral sequence reconstruction, synteny analyses, and multi-omics data. We found that around 16% of Meloidogyne genes are genus-specific transcribed orphan genes, with about 20% resulting from high divergence and 18% emerging de novo, often in transposon-rich genomic regions. Transcriptomic, translatomic, and proteomic evidence confirmed expression and translation of many orphan genes, which tend to encode shorter, secreted proteins. Notably, orphan genes are preferentially expressed during the infective juvenile stage and contribute substantially to the arsenal of nematode parasitism effectors. These findings highlight orphan genes as a significant and dynamic component of Meloidogyne genomes, potentially underpinning their parasitic adaptation and success.

bioinformatics↗

bioRxiv2025

Chromosome-scale genome assembly of Xiphinema index uncovers an unparalleled epigenetic toolkit in invertebrates

Nematodes constitute the most speciose animal phylum, occupying an exceptionally broad range of biomes and encompassing free-living microbe-feeders, predators, and notorious plant or animal parasites. However, the limited availability of genome-scale resources for early-branching nematode clades has constrained our understanding of the molecular determinants underlying these multiple evolutionary adaptations. Here, we present the genome of the plant-parasitic nematode Xiphinema index, constituting the first telomere-to-telomere assembly for the order Dorylaimida, an early-branching nematode lineage. Phylogenetic analyses reveal that horizontal gene transfers (HGT) have played a pivotal role in the emergence of plant parasitism in this phylum. Remarkably, we identify the first documented case of a plant-derived HGT in a nematode genome. This gene encodes a predicted secreted parasitic effector, underscoring the diversity of evolutionary events that contributed to the parasitic arsenal. Our results suggest that, beyond bacteria and fungi, plants themselves have provided crucial genes for parasitism that may now be used by the nematodes to manipulate them. Our comparative genomic analyses across more than 70 nematode species further uncover an unprecedented epigenetic toolkit in an invertebrate genome. Indeed, X. index harbors a complete set of canonical DNA methyltransferases, a full-length ATRX chromatin remodeler, and 3D-chromatin architectural CTCF protein coding homolog. Consistent with this repertoire, we detected methylation at CpG genome-wide, which inversely correlates with gene expression and chromatin accessibility. Together, these findings reveal a vertebrate-like epigenetic machinery in an early-branching nematode and call for a fundamental reassessment of the prevailing epigenetic paradigm in nematodes and, more broadly, in animals.

genomics↗