bioRxiv Science⌕ Search

SEARCH · bioRxiv Science

Results for “genomics”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources

Genomic analysis unveils the role of genome degradation events and gene flux in the emergence and persistence of S. Paratyphi A lineages

Paratyphoid fever caused by S. Paratyphi A is endemic in parts of Asia and Sub-Saharan Africa. The proportion of enteric fever cases caused by S. Paratyphi A has substantially increased, yet only limited data is available on the population structure and genetic diversity of this serovar. We examined the phylogenetic distribution and evolutionary trajectory of S. Paratyphi A isolates collected as part of the Indian enteric fever surveillance study "Surveillance of Enteric Fever in India (SEFI)." In the study period (2017-2020), S. Paratyphi A comprised 17.6% (441/2503) of total enteric fever cases in India, with the isolates highly susceptible to all the major antibiotics used for treatment except fluoroquinolones. Phylogenetic analysis clustered the global S. Paratyphi A collection into seven lineages (A-G), and the present study isolates were distributed in lineages A, C and F. Our analysis documented that the genome degradation events and gene acquisitions or losses play a major role in the evolution of new S. Paratyphi A lineages/sub-lineages. A total of 10 pseudogene-forming mutations possibly associated with the emergence of lineages were identified. Pan-genome analysis identified the insertion of P2/PSP3 phage and acquisition of IncX1 plasmid during the selection in 2.3.2/2.3.3 and 1.2.2 genotypes, respectively. We also identified that the six characteristic missense mutations associated with the lipopolysaccharide (LPS) biosynthesis genes of S. Paratyphi A confer only a low structural impact and would therefore have minimal impact on vaccine effectiveness. Since S. Paratyphi A is human restricted, high levels of genetic drift are not expected unless these bacteria transmit to naive hosts. However, public-health investigation and intervention by means of genomic surveillance would be continually needed to avoid S. Paratyphi A serovar becoming a public health threat similar to the S. Typhi of today.

genomics↗

Rapid genome functional annotation pipeline anchored to the House sparrow (Passer domesticus, Linnaeus 1758) genome reannotation

House sparrow (Passer domesticus) is an important avian model for both laboratory and field-based studies of evolutionary genetics, development, neurobiology, physiology, behavior, and ecology. The current annotation of the P. domesticus genome is available at Ensembl Rapid Release site, which currently only focuses on gene set building. Here, we provide the first functional reannotation of the P. domesticus genome based on enrichment with intestinal Illumina RNA-Seq libraries. This revised annotation describes 38592 transcripts, compared to 23574 currently for Ensembl, and 14717 predicted protein-coding genes, with 96.4% complete Passeriformes lineage BUSCOs. A key improvement in this revised annotation is the definition of untranslated region (UTR) sequences, with 82.7% and 93.8% of transcripts containing 5 and 3 UTRs, respectively. Our reannotation highlights the benefits to genome annotation improvement when additional specific RNA-Seq data is available for analysis and rapid data throughput (>200 Mb h-1) is used.

genomics↗

The International Weed Genomics Consortium: Community Resources for Weed Genomics Research

The International Weed Genomics Consortium is a collaborative group of researchers focused on developing genomic resources for the study of weedy plants. Weeds are attractive systems for basic and applied research due to their impacts on agricultural systems and capacity to swiftly adapt in response to anthropogenic selection pressures. Our goal is to use genomic information to develop sustainable and effective weed control methods and to provide insights about biotic and abiotic stress tolerance to assist crop breeding. Here, we outline resources under development by the consortium and highlight areas of research that will be impacted by these enabling resources.

genomics↗

Genome-wide assays to characterize rAAV integration into human genomic DNA in vivo

Adeno-associated viral (AAV) vectors are used to treat genetic diseases, expressing therapeutic genes from both extrachromosomal episomes and payloads that integrate into the host genome. Assays were developed to evaluate HR-mediated on-target integration and the potential occurrence of off-target integration. While many studies have addressed elements of these processes, proper characterization requires long-read sequencing to ensure that integrated viral DNA is examined and not the more prevalent episomes. We used Oxford Nanopore to characterize integrated DNA and scan the whole genome for off-target integrations. These assays were applied to cell-based and in vivo models to study vectors that correct phenylketonuria (PKU), caused by loss of phenylalanine hydroxylase (PAH). Administration of the human-specific vector in a humanized-liver mouse xenograft model resulted in stable, nuclease-free integration into PAH. Because detection of rare integration events in a much larger pool of episomal DNA is subject to artifacts, careful assay validation was required. A long-read, genome-wide assay capable of detecting on- and off-target vector integrations showed no evidence of off-target integration. Artifactual false positive events were below the limit of blank. These data support rAAV as an investigational therapeutic for genetic diseases and reinforce the need for characterization of integration assays to avoid artifacts.

genomics↗

Whole Genome Sequencing of DENV-2 isolated from Aedes aegypti mosquitoes in Esmeraldas, Ecuador. Genomic epidemiology of genotype III Southern Asian-American in the country.

Ecuador is a tropical country reporting Dengue virus (DENV) outbreaks with areas of hyperendemic viral transmission. Entomo-virological surveillance and monitoring effort conducted in the Northwestern border province of Esmeraldas in April 2022, five pools of female Aedes aegypti mosquitoes from a rural community tested positive for DENV serotype 2 by RT-qPCR. One pool was sequenced by Illumina MiSeq, and it corresponded to genotype III Southern Asian-American. Comparison with other genomes revealed genetic similarity to a human DENV genome sequenced in 2021, also from Esmeraldas. Potential introduction events to the country could have originated from Colombia, considering the vicinity of the collection sites to the neighboring country and high human movement. The inclusion of genomic information complements entomo-virological surveillance, providing valuable insights into genetic variants. This contribution enhances our understanding of Dengue virus (DENV) epidemiology in rural areas and guides evidence-based decisions for surveillance and interventions. Author SummaryIn this study, the complete genetic information of the dengue virus isolated from the mosquito vector Aedes aegypti was characterized using molecular biology, sequencing, and bioinformatics analysis. The isolation of the virus from the vector has contributed significantly to our understanding of the transmission dynamics of the disease and its genetic relationship with human cases. Identifying the serotypes and genotypes circulating in Ecuador has enabled us to comprehend the evolution of the virus from 2014 to 2023. Therefore, surveillance of genetic variability would aid in adapting precise prevention and control strategies to the genetic variants present in a specific geographical area. Entomo-virological surveillance is essential for assessing changes in risk and the impact of control measures.

genomics↗

Population-level whole genome sequencing of Ascochyta rabiei identifies genomic loci associated with isolate aggressiveness

Ascochyta blight caused by the ascomycete Ascochyta rabiei poses a major biotic threat to chickpea (Cicer arietinum) industries worldwide and incurs substantial costs to the Australian multimillion-dollar chickpea industry both in disease control and yield loss. The fungus was introduced to Australia in the 1970s from an unknown source population, and within a few decades, successfully established in all Australian agroecological chickpea growing regions. Although genetically highly clonal, a broad range of phenotypic variation in terms of aggressiveness exists among the Australian A. rabiei isolates. More recently, highly aggressive isolates capable of causing severe disease symptoms on moderate to highly resistant chickpea cultivars have increased in frequency. To identify genetic loci potentially associated with A. rabiei aggressiveness on Australian chickpea cultivars, we performed deep genome sequencing of 230 isolates collected from a range of agroecological chickpea growing regions between 2013 and 2020. Population genetic analyses using genome-wide single nucleotide polymorphism data identified three main clusters of genetically closely related isolates in Australia. Phylogenetic analyses showed that highly aggressive phenotypes developed multiple times independently throughout the phylogeny. Results point to minor contribution of multiple genetic regions and most likely epigenomic variations to aggressiveness of A. rabiei isolates on Australian chickpea cultivars. IMPACT STATEMENTThis research introduces new knowledge on the Australian A. rabiei population structure, molecular pathogenicity drivers and evolution as a clonal pathogen through comprehensive whole-genome sequencing approach. The knowledge generated on the structure and origin of the Australian A. rabiei and existence of only one mating type continues to inform researchers, growers, breeders and the broader industry on the importance for continued tight biosecurity measures and inform development of accurate and informed disease management and resistance breeding strategies. This research provides a rare real-life example to the effect of genetic drift on a clonal pathogen population and the importance of biosecurity to protect introduction from non-endemic isolates through seed importation in the current era of international markets. DATA SUMMARYAn online dataset containing the data and code required to reproduce the results found in this publication have been deposited at Zenodo (DOI 10.5281/zenodo.12575659). Isolate aggressiveness and collection metadata are available in the Ascochyta dashboard at http://bit.ly/asco-dashboard. Raw sequencing data used in this study was deposited to the NCBI Short Read Archive (SRA) and is available through BioProject PRJNA1175002. The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

genomics↗

Empirical Bayes spline model learns multi-way genomic interactions from single cell 3D genome data

A number of foundational analysis methods have emerged for single cell high throughput chromatin conformation (scHi-C) datasets capturing 3D organizations of genomes with pairwise measurements at the single cell or nuclei resolution; however, these datasets are currently under-utilized. The canonical analyses of scHi-C data encompass, beyond standard cell type identification, inference of chromosomal structures and pairwise interactions. However, multi-way chromatin interactions among genomic elements are entirely overlooked. We introduce MINTsC to learn Multi-way INTeractions from single cell Hi-C. MINTsC builds on a dirichlet-multinomial spline model and yields multi-way interaction scores by aggregating pairwise interactions across cells of a context and summarizing them using order statistics of pairwise test statistics. MINTsC yields well-calibrated p-values for controlling the false discovery rate. Evaluation of MINTsC with scHi-C datasets from cell lines and complex tissues using multiple external genomic and epigenomic datasets support multi-way interactions inferred by MINTsC. Application of MINTsC to scHi-C data from human prefrontal cortex revealed multi-way chromatin interactions with biological implications of gene regulation by multiple enhancers. Most notably, MINTsC-inferred multi-way interactions demonstrate its potential for probing molecular QTL and association studies for epistatic SNP effects by significantly reducing the multiple-testing burden. MINTsC is publicly available at https://github.com/keleslab/mintsc.

genomics↗

Genome-Wide Uncertainty-Moderated Extraction of Signal Annotations from Multi-Sample Functional Genomics Data

Multi-sample functional genomics experiments should reveal reproducible regulatory activity, but locus- and sample-specific noise can obscure biological signals in sequencing data. We introduce Consenrich for genome-wide estimation of epigenomic signals across multiple samples. To encourage robustness and sensitivity, the state-space model underlying Consenrich accounts for positional observation variances to determine shrinkage toward predictions from a smooth process model over genomic coordinates. We first apply Consenrich to ATAC-seq and ChIP-seq datasets and demonstrate its ability for robust signal recovery. We then utilize Consenrich upstream of a class-imbalanced differential accessibility analysis in an Alzheimer's cohort of twenty samples and show that it improves the breadth of relevant biological insights. Software is available at https://github.com/nolan-h-hamilton/Consenrich.

genomics↗

A Prelude to Conservation Genomics: First Chromosome-Level Genome Assembly of a Flying Squirrel (Pteromyini: Pteromys volans)

The Siberian flying squirrel (Pteromys volans) represents the only European Pteromyini species. Thus, it is biogeographically unique due to its specialised anatomy and biology as a volant rodent. As a result of habitat fragmentation and destruction, Siberian flying squirrels experience severe and ongoing population declines throughout most of their distribution. While considered Least Concern throughout their immense Eurasian distribution, this species is red-listed as Vulnerable and even Critically Endangered in parts of its range. More knowledge about the population structure and overall biology is needed to improve conservation efforts for this umbrella and flagship species of old-growth boreal forests. Here, we present the first chromosome-level genome assembly of any Pteromyini, represented by P. volans (Uoulu_pteVol_1.0). The final assembly has a total length of 2.85 Gbp in 19 chromosome-scale scaffolds with only minor differences in the chromosomal structure compared to other Sciuridae. All chromosome-scale scaffolds show indications for telomeres at both ends; the N50 value and busco as well as k-mer completeness scores are high with 157.39 Mbp and 97 - 99 %, respectively, indicating chromosome-level quality of the assembly. Based on whole-genome data from 17 rodent species, P. volans clusters according to known evolutionary relationships. Additionally, we present a new 16,511 bp long mitogenome unveiling differences from known conspecific mitogenomes. We propose the utility of the new reference genome for further research and development of conservation-applied genetic methods.

genomics↗

Unraveling the Genomic and Phylogenetic Complexity of the understudied microfungus Basidiobolus: Insights from 19 Newly Sequenced Genomes

Basidiobolus is a globally distributed genus of early-diverging fungi within Zoopagomycota, known for its presence in diverse ecological niches ranging from soil and decaying organic matter to vertebrate gastrointestinal tracts. Despite its ecological and medical relevance, the taxonomy and evolutionary relationships within the genus remain poorly resolved due to limited genomic resources. In this study, we present nineteen newly sequenced Basidiobolus genomes, expanding the available genomic data. Using short-read Illumina sequencing, assembly, and annotation pipelines, we characterize genic content, assess completeness, and explore biosynthetic gene content across isolates. Phylogenomic analysis reveals two major clades corresponding to B. meristosporus and B. ranarum, while B. heterosporus forms a distinct lineage. Several isolate clusters exhibit deep divergence suggestive of cryptic species, underscoring the need for expanded sampling and taxonomic revision. Functional annotations reveal a rich repertoire of biosynthetic gene clusters, including non-ribosomal peptide synthetases, polyketide synthases, and hybrid clusters, pointing to an underexplored reservoir of secondary metabolite diversity. These findings position Basidiobolus as a compelling model for investigating fungal evolution, ecological adaptation, and natural product biosynthesis.

genomics↗

The Consortium for Genomic Diversity, Ancestry, and Health in Colombia (CODIGO): building local capacity in genomics, bioinformatics, and precision medicine

The Consortium for Genomic Diversity, Ancestry, and Health in Colombia (CODIGO) aims to build a community of Colombian researchers in support of local capacity in genomics, bioinformatics, and precision health. Here, we present the first CODIGO data release and the consortium web platform, including annotations for more than 95 million genetic variants from 1,441 samples representing 14 populations from across the country. CODIGO samples show a wide range of African (16.7%), European (50.6%), and Indigenous American (32.8%) genetic ancestry components, with five distinct ancestry clusters. Thousands of ancestry-enriched variants, with divergent allele frequencies across clusters, show pharmacogenomic and clinical genetic associations. Examples include African ancestry-enriched variants associated with fast metabolism of the immunosuppressive drug tacrolimus and malaria resistance and European ancestry-enriched variants associated with nicotine dependence and hereditary hemochromatosis. CODIGO reveals the nexus between ancestry and health in Colombia and underscores the utility of collaborative genome sequence analysis efforts.

genomics↗

Genome structure mapping with high-resolution 3D genomics and deep learning

Gene expression is often regulated by distal enhancers through cell-type-specific 3D looping interactions, but compre-hensive mapping of these interactions across cell types is experimentally intractable. To address this gap, we introduce an integrated approach where we generate ultra-deep Region Capture Micro-C (RCMC) and Micro-C data specifically designed for state-of-the-art deep learning architectures. We developed Cleopatra, an attention-based deep learning model that takes epigenomic inputs and is pre-trained on genome-wide Micro-C data followed by fine-tuning with high-resolution RCMC data. Cleopatra accurately predicts 3D maps at sub-kilobase bin sizes and unprecedented resolution, enabling us to generate ultra-high-resolution, genome-wide 3D contact maps across four human cell types. These maps revealed cell-type-specific microcompartments and over 900,000 loops across the cell types, about half of which are cell-type-specific. Using Cleopatra maps, we observe that promoters form about a dozen loops on average, and that expression increases monotonically with the number of loops, indicating that looping is associated with higher gene expression. We further show the enhancer-promoter loops are often anchored by CTCF, and nominate new transcription factors that may regulate cell-type-specific enhancer-promoter interactions. Overall, we establish a framework for ultra-high-resolution 3D genome mapping, providing a broadly applicable resource for gaining new insights into cell-type-specific gene regulation.

genomics↗

Mitochondrial Genome of the lesser known - Madras Hedgehog (Paraechinus nudiventris): Genomic characterization and comparative analysis within Erinaceidae

The Madras hedgehog (Paraechinus nudiventris) is an understudied species endemic to southern India, with limited genetic data available for understanding its evolutionary history. Here, we present the complete mitochondrial genome (17,232 bp), annotated and analyzed in comparison with other Erinaceidae species. The mitogenome retains the typical vertebrate structure, comprising 14 protein-coding genes, 22 tRNAs, 2 rRNAs, and a non-coding control region, with an A+T rich nucleotide composition. Phylogenetic analyses using Bayesian and maximum likelihood approaches confirmed the species placement within Paraechinus, with divergence from P. micropus estimated during the Pleistocene. Molecular evolutionary analyses revealed selective constraints on oxidative phosphorylation genes, with atp8 showing the highest variability. Our divergence time estimates, incorporating fossil calibrations, refine the evolutionary timeline of Erinaceidae, providing insights into the diversification of hedgehogs in South Asia. By making this annotated mitochondrial genome publicly available, we provide a foundational resource for future studies on the genetic diversity, phylogeography, and conservation of P. nudiventris and its relatives. The study also demonstrates the utility of non-invasive sampling methods in generating high-quality genomic data for cryptic mammalian species.

genomics↗

The FORGENIUS genomic resources: new genotyping tools and genomic data for 23 forest tree species and their Genetic Conservation Units

Genetic diversity is a critical but often overlooked component of biological diversity. The European H2020 FORGENIUS project is precisely aimed at increasing the quality and quantity of genetic data to start monitoring the European network of forest Genetic Conservation Units (GCUs). A first step in this direction was developing standardized genomic resources for 23 forest tree species, spanning from rare and scattered (e.g., Abies nebrodensis and Torminalis glaberrima) to widespread, economically relevant ones (e.g., Fagus sylvatica, Picea abies and Pinus sylvestris). Here, we describe the development and application of targeted genotyping tools, primarily based on Single Primer Enrichment Technology (SPET), along with existing SNP arrays for the selected species. The SPET panels developed in FORGENIUS were designed to capture {square}10,000 loci per species, balancing species-specific and randomly distributed regions to ensure broad genome coverage and minimize ascertainment bias. Across 7,192 genotyped trees, we identified over 1.8 million single nucleotide polymorphisms (SNPs) covering approximately 50 Mb of DNA sequence. SPET panels demonstrated high genotyping efficiency and cross-species transferability, especially within genera such as Quercus and Abies. They represent a cost-effective, flexible, and scalable solution for population-level genetic assessments across diverse taxa, enabling standardized, genome-wide characterization of the GCU network. These resources not only promote the establishment of genetic monitoring, support genetically informed conservation strategies and improve our understanding of adaptive responses in European forests, but also enhance species delimitation and hybrid detection, and enable the characterization of phylogenetically related but previously underexplored species.

genomics↗

Insights from farming Macrocystis pyrifera offshore: phenotypic analysis, genome-wide association studies, genomic selection

Seaweed farming, as a part of aquaculture, offers a sustainable alternative to modern agricultural practices; however, genetic enhancement and breeding programs for most species are underdeveloped. We aimed to advance seaweed domestication by focusing on giant kelp (Macrocystis pyrifera), the fastest-growing haplodiplontic brown alga, which has significant ecological and commercial importance. We analyzed phenotypic data from two offshore experimental farms conducted in 2019 and 2020, which involved hundreds of outplanted genetically diverse sporophytes. We found that outplanting season and farm design had significant effects on giant kelp biomass. Broad-sense heritability estimates showed moderate (0.27-0.50) genetic contributions to two phenotypes, carbon content and total biomass. Genome-wide association studies for these phenotypes resulted in three statistically significant SNPs, located near or within genes involved in carbohydrate metabolism and cytoskeletal functions. In addition, we applied genomic selection models that integrated sporophyte phenotypes and parental gametophyte genotypes. These models utilized reduced sets of GWAS-ranked SNPs obtained by a procedure based on linkage disequilibrium estimations. Model testing yielded cross-validation accuracy values of up to 0.84 and predictive accuracy values of up to 0.40, demonstrating the potential of marker-assisted breeding for phenotype improvement. Our results provide foundational genomic resources and tools for domesticating and breeding M. pyrifera, offering a basis for developing giant kelp varieties with desirable traits.

genomics↗

Whole-genome resequencing and pan-transcriptome reconstruction highlight the impact of genomic structural variation on secondary metabolism gene clusters in the grapevine Esca pathogen Phaeoacremonium minimum

The Ascomycete fungus Phaeoacremonium minimum is one of the primary causal agents of Esca, a widespread and damaging grapevine trunk disease. Variation in virulence among Pm. minimum isolates has been reported, but the underlying genetic basis of the phenotypic variability remains unknown. The goal of this study was to characterize intraspecific genetic diversity and explore its potential impact on virulence functions associated with secondary metabolism, cellular transport, and cell wall decomposition. We generated a chromosome-scale genome assembly, using single molecule real-time sequencing, and resequenced the genomes and transcriptomes of multiple isolates to identify sequence and structural polymorphisms. Numerous insertion and deletion events were found for a total of about 1 Mbp in each isolate. Structural variation in this extremely gene dense genome frequently caused presence/absence polymorphisms of multiple adjacent genes, mostly belonging to biosynthetic clusters associated with secondary metabolism. Because of the observed intraspecific diversity in gene content due to structural variation we concluded that a transcriptome reference developed from a single isolate is insufficient to represent the virulence factor repertoire of the species. We therefore compiled a pan-transcriptome reference of Pm. minimum comprising a non-redundant set of 15,245 protein-coding sequences. Using naturally infected field samples expressing Esca symptoms, we demonstrated that mapping of meta-transcriptomics data on a multi-species reference that included the Pm. minimum pan-transcriptome allows the profiling of an expanded set of virulence factors, including variable genes associated with secondary metabolism and cellular transport.

genomics↗

Stout camphor tree genome fills gaps in understanding of flowering plant genome and gene family evolution

We present reference-quality genome assembly and annotation for the stout camphor tree (SCT; Cinnamomum kanehirae [Laurales, Lauraceae]), the first sequenced member of the Magnoliidae comprising four orders (Laurales, Magnoliales, Canellales, and Piperales) and over 9,000 species. Phylogenomic analysis of 13 representative seed plant genomes indicates that magnoliid and eudicot lineages share more recent common ancestry relative to monocots. Two whole genome duplication events were inferred within the magnoliid lineage, one before divergence of Laurales and Magnoliales and the other within the Lauraceae. Small scale segmental duplications and tandem duplications also contributed to innovation in the evolutionary history of Cinnamomum. For example, expansion of terpenoid synthase subfamilies within the Laurales spawned the diversity of Cinnamomum monoterpenes and sesquiterpenes.

genomics↗

Population genomic structure and genome-wide linkage disequilibrium in farmed Atlantic salmon (Salmo salar L.) using dense SNP genotypes

Chilean Farmed Atlantic salmon (Salmo salar) populations were established with individuals of both European and North American origins. These populations are expected to be highly genetically differentiated due to evolutionary history and poor gene flow between ancestral populations from different continents. The extent and decay of linkage disequilibrium (LD) among single nucleotide polymorphism (SNP) impacts the implementation of genome-wide association studies and genomic selection and provides relevant information about demographic processes of fish populations. We assessed the population structure and characterized the extent and decay of LD in three Chilean commercial populations of Atlantic salmon with North American (NAM), Scottish (SCO) and Norwegian (NOR) origin. A total of 151 animals were genotyped using a 159K SNP Axiom(R) myDesign Genotyping Array. A total of 40K, 113K and 136 K SNP markers were used for NAM, SCO and NOR populations, respectively. The principal component analysis explained 86.7% of the genetic diversity between populations, clearly discriminating between populations of North American and European origin, and also between European populations. Admixture analysis showed that the Scottish and North American populations likely come from one ancestral population, while the Norwegian population probably originated from more than one. NAM had the lowest effective size, followed by SCO and NOR. Large differences in the LD decay were observed between populations of North American and European origin. A r2 threshold of 0.2 was estimated for marker pairs separated by 8,000 Kb, 42 and 64 Kb in the NAM, NOR and SCO populations, respectively. In this study we show that this SNP panel can be used to detect association between markers and traits of interests and also to capture high-resolution information for genome-enabled predictions. Also, we suggest the feasibility to achieve higher prediction accuracies by using a small SNP data set as was used with the NAM population.

genomics↗