Biology subjects

Paulin, L.

Publications and source records attributed to Paulin, L..

14 recordsLinked to original sources

bioRxiv2026

Long-read sequencing maps transposable element variation and its regulatory and epigenetic effects in the human brain

Transposable elements (TEs) are mobile DNA sequences that shape genome architecture and gene regulation, yet their roles in the human brain remain largely unresolved. Short-read sequencing lacks the resolution to accurately map TE insertions, detect associated structural variants, and resolve highly repetitive regions. Here, we leverage long-read whole-genome sequencing to profile germline TE insertions in postmortem brain tissue from two ancestrally diverse cohorts: the North American Brain Expression Consortium (NABEC; European ancestry, n = 205) and the Human Brain Collection Core (HBCC; African and African-admixed ancestry, n = 146). We identified 2,842 and 1,660 high-confidence non-reference insertions in HBCC and NABEC, respectively, spanning Alu, LINE-1, and SVA elements. We then also further characterized complex short tandem repeat and variable number tandem repeat variation within reference SVA and Alu loci. Reference TEs were also found to mediate complex structural variants at loci implicated in brain development and neurodegenerative disease, with several showing ancestry-specific patterns. Integration of bulk RNA-sequencing data identified TE expression quantitative trait loci, including insertions that modulate neuronal gene expression. Single-nucleus RNA sequencing revealed cell-type-specific effects of TE regulation across cortical populations. Long-read methylation profiling further demonstrated age-associated epigenetic regulation of both reference and non-reference Alu elements. As a community resource, we release a catalog of TE insertions, allele frequencies, and ancestry-specific distributions to enable future functional and disease-focused investigations. Together, these findings highlight the widespread regulatory and epigenetic influence of TEs in the human brain and establish long-read sequencing as a powerful approach for uncovering cell-type- and population-specific TE dynamics.

genomics↗

bioRxiv2026

A systematic assessment of machine learning for structural variant filtering

BackgroundAccurate discrimination of true structural variants (SVs) from artifacts in long-read sequencing data remains a critical bottleneck. Numerous machine learning solutions have been proposed, ranging from classical models using engineered features to advanced deep learning and foundation model interpretability methods. However, a systematic comparison of their performance, efficiency, and practical utility is lacking. ResultsWe conducted a comprehensive benchmark of five machine learning paradigms for SV filtering using standardized Genome in a Bottle (GIAB) data for samples HG002 and HG005. We evaluated classical Random Forest classifiers on 15 genomic features, computer vision models (ResNet/VICReg), diffusion-based anomaly detection, sparse autoencoders (SAEs) on the Evo2-7B foundation model, and multimodal ensembles. A simple Random Forest on interpretable features achieved a peak F1-score of 95.7%, effectively matching all more complex models (ResNet50: 95.9%, Diffusion: 95.8%). This study represents the first application of diffusion-based anomaly detection and sparse autoencoders to structural variant analysis; while diffusion models learned highly discriminative, disentangled representations and SAEs uncovered biologically interpretable features (including atoms that were specific for ALU deletions, chromosome X variants and insertion events), they did not significantly surpass this classification ceiling. Ensemble methods offered no performance benefit but may have future potential given the orthogonality of vision-based and linear features. ConclusionsOur findings demonstrate that for the established task of germline SV filtering, simpler, interpretable models provide an optimal balance of accuracy, speed, and transparency. This benchmark establishes a pragmatic framework for method selection and argues that increased model complexity must be justified by clear, unmet biological needs rather than marginal predictive gains.

bioinformatics↗

bioRxiv2023

Comparison of phage and plasmid populations present in the gut microbiota of Parkinson's disease patients

The aging population worldwide is on the rise, leading to a higher number of Parkinsons disease (PD) cases each year. PD is presently the second most prevalent neurodegenerative disease, affecting an estimated 7-10 million individuals globally. This research aimed to identify mobile genetic elements in human fecal samples using a shotgun metagenomics approach. We found over 44,000 plasmid contigs and compared plasmid populations between PD patients (n = 68) and healthy controls (n = 68). Significant associations emerged between Body Mass Index (BMI) and plasmid alpha diversity. Moreover, the gene populations present on plasmids displayed marked differences in alpha and beta diversity between PD patients and healthy controls. We identified a considerable number of phage contigs that were differentially abundant in the two groups. Moreover, we improved the continuity and identification of the protein coding regions of the phage contigs by implementing alternative genetic codes. We built a classification system based on a selection of the phages differentially abundant in the groups. A machine learning approach based on phage abundances allowed a classification of the subjects into the PD or control group with an area under curve (AUC) of 0.969.

microbiology↗

bioRxiv2023

Metagenome-assembled microbial genomes from Parkinson's disease fecal samples

The human gut microbiome composition has been linked to Parkinsons disease (PD). However, knowledge of the gut microbiota on the genome level is still limited. Here we performed deep metagenomic sequencing and binning to build metagenome-assembled genomes (MAG) from 136 human fecal microbiomes (68 PD samples and 68 control samples). We constructed 952 non-redundant high-quality MAGs and compared them between PD and control groups. Among these MAGs, there were 22 different versions of Collinsella and Prevotella MAGs, indicating high variability of those genera in the human gut environment. Microdiversity analysis indicated that Ruminococcus bromii was statistically significantly (p < 0.002) more diverse on the strain level in the control samples compared to the PD samples. In addition, by clustering all genes and performing presence-absence analysis between groups, we identified several control-specific (p < 0.05) related genes, such as speF and Fe-S oxidoreductase. We also report detailed annotation of MAGs, including Clusters of Orthologous Genes (COG), Cas operon type, antiviral gene, prophage, and secondary metabolites biosynthetic gene clusters, which can be useful for providing a reference for future studies.

genomics↗

bioRxiv2023

Transcriptome analysis reveals novel regulators of the Scots pine stilbene pathway

Stilbenes are developmentally induced metabolites in Scots pine heartwood where they have important role in protecting wood from decaying fungi. The stilbene pathway is also stress inducible, and ultraviolet (UV)-C radiation was among the first discovered artificial stress activators of the pathway. Many conditions that activate the pathway are known, but the specific transcriptional regulators and the biosynthetic enzyme responsible for activating the stilbene precursor cinnamate in the pathway are unknown. Here we describe the first large-scale transcriptomic analysis of pine needles in response to UV-C exposure and treatment with translational inhibitor cycloheximide, both activating the transcription of stilbene pathway genes, to uncover the candidates for the transcriptional regulation of the pathway and the cinnamate activating CoA ligase. We show that the regulation of pine stilbene pathway has shared features with grapevine stilbene pathway. In both species, the stilbene pathway was transcriptionally activated after UV-C treatment, protein phosphatase inhibitors and plant hormones ethylene and jasmonate. The pine stilbene synthase promoter retains its inducibility when transformed in plants that normally do not synthesize stilbenes. Pine stilbene synthase promoter was able to activate the expression of a reporter gene in Arabidopsis in response to UV-C exposure and phosphatase inhibitors, but not as response to plant hormone treatment. This indicates that stilbene synthase gene regulation occurs both via ancient stress-response pathway(s) but also via species specific regulators. With transcriptomic approach we identified candidate enzymes for cinnamate acting CoA ligase and transcription factors regulating the pathway.

plant biology↗

bioRxiv2022

Fragmented habitat compensates for the adverse effects of genetic bottleneck

In the face of human-caused biodiversity crisis, understanding the theoretical basis of conservation efforts of endangered species and populations has become increasingly important. According to population genetics theory, population subdivision helps organisms retain genetic diversity, crucial for adaptation in a changing environment. Habitat shape is thought to be important for generating and maintaining population subdivision, but empirical cases are needed to test this assumption. We studied Saimaa ringed seals, landlocked in a labyrinthine lake and recovering from a drastic bottleneck, by whole-genome sequencing 105 individuals and additional individuals from three other ringed seal subspecies. We analyzed the distribution of variation and genetic relatedness among the individuals in relation to the habitat shape. Despite a severe history of a genetic bottleneck with prevalent homozygosity in Saimaa ringed seals, we found evidence for population structure mirroring the subregions of the lake. Highlighting the significance of habitat connectivity in conservation biology and the power of genomic tools in understanding its impact, genome-wide analyses showed that the subpopulations had retained unique variation and largely complementary patterns of homozygosity. Integration of genetic analyses in conservation decisions gives hope to Saimaa ringed seals and other endangered species in fragmented habitats.

evolutionary biology↗

bioRxiv2021

Convergent evolution of mevalonate pathway in Inonotus obliquus and Betula pendula.

Inonotus obliquus, Chaga mushroom, is a fungal species from Hymenochaetaceae family (Basidiomycota) which has been widely used for traditional medicine in Europe and Asia. Here, chaga genome was sequenced using Pacbio sequencing into a 50.7Mbp assembly consisting of 301 primary contigs with an N50 value of 375 kbp. Genome evolution analyses revealed a lineage-specific whole genome duplication event and an expansion of Cytochrome P450 superfamily. Fungal biosynthetic clusters were enriched for tandemly duplicated genes, suggesting that biosynthetic pathway evolution has proceeded through small-scale duplications. Metabolomic fingerprinting confirmed a highly complex terpene biosynthesis chemistry when compared against related fungal species lacking the genome duplication event.

evolutionary biology↗

bioRxiv2021

A Taphrina strain infecting the model plant Arabidopsis thaliana.

Yeasts are important plant-associated organisms that can modulate host immunity to either promote or prevent disease. Mechanisms of plant-yeast interactions, specifically of yeast perception by the plant innate immune system, remain unknown. Progress has been hindered by the scarcity of yeast species associated with the model plant Arabidopsis thaliana (Arabidopsis). We have previously isolated Taphrina strain M11 from wild Arabidopsis in the field. Taphrina are poorly studied dimorphic yeast-like fungi that are plant pathogens, often producing plant hormones and causing tumour-like and leaf deformation symptoms on their hosts. Here we characterize the interaction of M11 with Arabidopsis. Infection of Arabidopsis with the birch pathogen T. betulina, used as a non-host control, shows early HR, enhanced ROS accumulation, and limitation of growth, demonstrating that Arabidopsis had immunity against non-adapted yeasts. M11 triggered limited cell death, an attenuated ROS response, and grew in planta, as well as subtle but clear leaf deformation symptoms, demonstrating it is pathogenic. Hormone responsive promoter-reporter analysis demonstrated activation of cytokinin signalling during infection. Mutant infection assays indicate jasmonate and ethylene were required for immunity against M11. Analysis of the Taphrina M11 genome was used to mine evidence for yeast specific PAMPs which may underlie host immune responses against yeast-like fungi.

plant biology↗

bioRxiv2020

Improved chromosome level genome assembly of the Glanville fritillary butterfly (Melitaea cinxia) based on SMRT Sequencing and linkage map.

The Glanville fritillary (Melitaea cinxia) butterfly is a long-term model system for metapopulation dynamics research in fragmented landscapes. Here, we provide a chromosome level assembly of the butterflys genome produced from Pacific Biosciences sequencing of a pool of males, combined with a linkage map from population crosses. The final assembly size of 484 Mb is an increase of 94 Mb on the previously published genome. Estimation of the completeness of the genome with BUSCO, indicates that the genome contains 93 - 95% of the BUSCO genes in complete and single copies. We predicted 14,830 gene models using the MAKER pipeline and manually curated 1,232 of these gene models. The genome and its annotated gene models are a valuable resource for future comparative genomics, molecular biology, transcriptome and genetics studies on this species.

genomics↗

bioRxiv2020

Genetic screen to saturate guard cell signaling network reveals a role of GDP-L-fucose metabolism in stomatal closure

Guard cells regulate plant gas exchange by controlling the aperture of stomatal pores. The process of stomatal closure involves a multi-input signaling network that governs the activity of ion channels, which in turn regulate guard cell turgor pressure and volume. Here we describe a forward genetic screen to identify novel components involved in stomatal movements. Through an ozone-sensitivity approach combined with whole-rosette gas exchange analysis, 130 mutants of established stomatal regulators and 76 novel mutants impaired in stomatal closure were identified. One of the novel mutants was mapped to MURUS1 (MUR1), the first enzyme in de novo GDP-L-fucose biosynthesis. Defects in synthesis or import of GDP-L-Fuc into the Golgi apparatus resulted in impaired stomatal closure to multiple stimuli. Stomatal phenotypes observed in mur1 were independent from the canonical guard cell signaling and instead could be related to altered mechanical properties of guard cell walls. Impaired fucosylation of xyloglucan, N-linked glycans and arabinogalactan proteins did not explain the aberrant function of mur1 stomata, however our data suggest that the stomatal phenotypes observed in mur1 can at least partially be attributed to defective dimerization of rhamnogalactouronan-II. In addition to providing the genetic framework for future studies on guard cell signaling, our work emphasizes the impact of fucose metabolism on stomatal movement.

plant biology↗

bioRxiv2019

A comparative and functional genomics analysis of the genus Romboutsia provides insight into adaptation to an intestinal lifestyle

Cultivation-independent surveys have shown that the recently described genus Romboutsia within the family Peptostreptococcaceae is more diverse than previously acknowledged. The majority of Romboutsia-associated 16S rRNA gene sequences have an intestinal origin, but the specific roles that Romboutsia species play in the digestive tract are largely unknown. The complete genomes of the human intestinal isolate Romboutsia hominis FRIFIT (DSM 28814) and the soil isolate Romboutsia lituseburensis A25KT (DSM 797) were sequenced. An evaluation of the common traits of this recently defined genus was done based on comparative genome analysis of the two strains together with the previously elucidated genome of the type species Romboutsia ilealis CRIBT. These analyses showed that the genus Romboutsia covers a broad range of metabolic capabilities with respect to carbohydrate utilization, fermentation of single amino acids, anaerobic respiration and metabolic end products. Main differences between strains were found in their abilities to utilize specific carbohydrates, to synthesize vitamins and other cofactors, and their nitrogen assimilation capabilities. In addition, differences were found with respect to bile metabolism and motility-related gene clusters.

microbiology↗

bioRxiv2019

Life history genomic regions explain differences in Atlantic salmon marine diet specialization

O_LIAnimals employ various foraging strategies along their ontogeny to acquire energy, and with varying degree of efficiencies, to support growth, maturation and subsequent reproduction events. Individuals that can efficiently acquire energy early are more likely to mature at an earlier age, as a result of faster energy gain which can fuel maturation and reproduction. C_LIO_LIWe aimed to test the hypothesis that heritable resource acquisition variation that co-varies with efficiency along the ontogeny would influence maturation timing of individuals. C_LIO_LITo test this hypothesis, we utilized Atlantic salmon as a model which exhibit a simple, hence trackable, genetic control of maturation age. We then monitored the variation in diet acquisition (quantified as the stomach fullness and composition) of individuals with different ages, and linked it genomic regions (haploblocks) that were previously identified to be associated with age-at-maturity. C_LIO_LIConsistent with the hypothesis, we demonstrated that one of the life history genomic regions tested (six6) was indeed associated with age-dependent differences in stomach fullness. Prey composition was marginally linked to both genomic regions (six6 and vgll3). We further showed Atlantic salmon switched to the so-called "feast and famine" strategy along the ontogeny, where older age groups exhibited heavier stomach content, but that came at the expense of running on empty more often. C_LIO_LIThese results suggest genetic variation underlying resource utilization variation may explain the genetic basis of age structure in Atlantic salmon. Given that ontogenetic diet has a genetic component and the strong spatial diversity associated with these genomic regions, we predict populations with diverse maturation age will have diverse evolutionary responses to future changes in marine food-web structures. C_LI

ecology↗

bioRxiv2019

A novel phyllosphere resident Protomyces species that interacts with the Arabidopsis immune system.

We describe the genome contents of six Protomyces spp. that are pathogenic within the typical host range of the genus and a novel Protomyces strain (SC29) that was previously isolated from the phylloplane of wild Arabidopsis thaliana (Arabidopsis), an atypical or possible alternate host. Genome-wide phylogenetic analysis defined SC29 as a distinct Protomyces sp. Analysis of gene family expansions, gene retention, and gene loss patterns among these Protomyces spp. lead us to hypothesize that SC29 may have undergone a host jump. The role of phyllosphere residency in the lifecycle of Protomyces spp. was previously unknown. Genomic changes in SC29 and all other Protomyces spp. were consistent with adaptations to the plant phylloplane. As predicted by our analysis of its mating locus, SC29 did not cause disease on Arabidopsis as a single strain, but could persist in its phylloplane, while the closely related P. inouyei does not. SC29 treated Arabidopsis exhibited enhanced immunity against Botrytis cinerea infection, associated with activation of MAPK3/6, camalexin, and SA-signalling pathways. We conclude that SC29 is a novel Protomyces sp. able to survive in the Arabidopsis phylloplane and that phylloplane residency is an important element in the lifecycle of Protomyces spp.

microbiology↗

bioRxiv2018

Bracketing phenotypic limits of mammalian hybridization

An increasing number of mammalian species have been shown to have a history of hybridization and introgression based on genetic analyses. Only relatively few fossils, however, preserve genetic material and morphology must be used to identify the species and determine whether morphologically intermediate fossils could represent hybrids. Because dental and cranial fossils are typically the key body parts studied in mammalian paleontology, here we bracket the potential for phenotypically extreme hybridizations by examining uniquely preserved cranio-dental material of a captive hybrid between gray and ringed seals. We analyzed how distinct these species are genetically and morphologically, how easy it is to identify the hybrids using morphology, and whether comparable hybridizations happen in the wild. We show that the genetic distance between these species is more than twice the modern human-Neanderthal distance, but still within that of morphologically similar species-pairs known to hybridize. In contrast, morphological and developmental analyses show gray and ringed seals to be highly disparate, and that the hybrid is a predictable intermediate. Genetic analyses of the parent populations reveal introgression in the wild, suggesting that gray-ringed seal hybridization is not limited to captivity. Taken together, gray and ringed seals appear to be in an adaptive radiation phase of evolution, showing large morphological differences relative to their comparatively modest genetic distance. Because morphological similarity does not always correlate with genetic distance in nature, we postulate that there is considerable potential for mammalian hybridization between phenotypically disparate taxa.

evolutionary biology↗