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Explore bioRxiv genomics preprints on sequencing, gene expression and genetic variation. Read source abstracts and verify methods in the manuscript; preprints are not peer reviewed.

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bioRxiv2023

High genomic plasticity and unique features of Xanthomonas translucens pv. graminis revealed through comparative analysis of complete genome sequences

BackgroundXanthomonas translucens pv. graminis (Xtg) is a major bacterial pathogen of economically important forage grasses, causing severe yield losses. So far, genomic resources for this pathovar consisted mostly of draft genome sequences, and only one complete genome sequence was available, preventing comprehensive comparative genomic analyses. Such comparative analyses are essential in understanding the mechanisms involved in the virulence of pathogens and to identify virulence factors involved in pathogenicity. ResultsIn this study, we produced high-quality, complete genome sequences of four strains of Xtg, complementing the recently obtained complete genome sequence of the Xtg pathotype strain. These genomic resources allowed for a comprehensive comparative analysis, which revealed a high genomic plasticity with many chromosomal rearrangements, although the strains were highly related, with 99.9 to 100% average nucleotide identity. A high number of transposases were exclusively found in Xtg and corresponded to 413 to 457 insertion/excision transposable elements per strain. These mobile genetic elements are likely to be involved in the observed genomic plasticity and may play an important role in the adaptation of Xtg. The pathovar was found to lack a type IV secretion system, and it possessed the smallest set of type III effectors in the species. However, three XopE and XopX family effectors were found, while in the other pathovars of the species two or less were present. Additional genes that were specific to the pathovar were identified, including a unique set of minor pilins of the type IV pilus, 17 TonB-dependent receptors (TBDRs), and 11 degradative enzymes. ConclusionThese results suggest a high adaptability of Xtg, conferred by the abundance of mobile genetic elements, which may have led to the loss of many features. Conserved features that were specific to Xtg were identified, and further investigation will help to determine genes that are essential to pathogenicity and host adaptation of Xtg.

plant biology↗
bioRxiv2023

A genome-wide single-cell 3D genome atlas of lung cancer progression

Although three-dimensional (3D) genome structures are altered in cancer cells, little is known about how these changes evolve and diversify during cancer progression. Leveraging genome-wide chromatin tracing to visualize 3D genome folding directly in tissues, we generated 3D genome cancer atlases of murine lung and pancreatic adenocarcinoma. Our data reveal stereotypical, non-monotonic, and stage-specific alterations in 3D genome folding heterogeneity, compaction, and compartmentalization as cancers progress from normal to preinvasive and ultimately to invasive tumors, discovering a potential structural bottleneck in early tumor progression. Remarkably, 3D genome architectures distinguish histologic cancer states in single cells, despite considerable cell-to-cell heterogeneity. Gene-level analyses of evolutionary changes in 3D genome compartmentalization not only showed compartment-associated genes are more homogeneously regulated, but also elucidated prognostic and dependency genes in lung adenocarcinoma and a previously unappreciated role for polycomb-group protein Rnf2 in 3D genome regulation. Our results demonstrate the utility of mapping the single-cell cancer 3D genome in tissues and illuminate its potential to identify new diagnostic, prognostic, and therapeutic biomarkers in cancer.

cell biology↗
bioRxiv2024

Improving genomic selection in hexaploid wheat with sub-genome additive and epistatic models

The goal of wheat breeding is the development of superior cultivars tailored to specific environments, and the identification of promising crosses is crucial for the success of breeding programs. Although genomic estimated breeding values were developed to estimate additive effects of genotypes before testing as parents, application has focused on predicting performance of candidate lines, ignoring non-additive genetic effects. However, non-additive genetic effects are hypothesized to be especially importance in allopolyploid species due to the interaction between homeologous genes. The objectives of this study were to model additive and additive-by-additive epistatic effects to better delineate the genetic architecture of grain yield in wheat and to the improve accuracy of genomewide predictions. The dataset utilized consisted of 3740 F5:6 experimental lines tested in the K-State wheat breeding program across the years 2016 and 2018. Covariance matrices were calculated based on whole and sub-genome marker data and the natural and orthogonal interaction approach (NOIA) was used to estimate variance components for additive and additive-by-additive epistatic effects. Incorporating epistatic effects in additive models resulted in non-orthogonal partitioning of genetic effects but increased total genetic variance and reduced deviance information criteria. Estimation of sub-genome effects indicated that genotypes with the greatest whole genome effects often combine sub-genomes with intermediate to high effects, suggesting potential for crossing parental lines which have complementary sub-genome effects. Modeling epistasis in either whole-genome or sub-genome models led to a marginal (3%) but significant improvement in genomic prediction accuracy, which could result in significant genetic gains across multiple cycles of breeding.

genetics↗
bioRxiv2024

Chromosome-level genome assembly of autotetraploid Selenicereus megalanthus and gaining genomic insights into the evolution of trait patterning in diploid and polyploid pitaya species

Yellow pitaya (Selenicereus megalanthus, 2n=4x=44) breeding remains severely hindered due to lacking a reference genome. Here we report yellow pitayas high-quality chromosome-level genome assembly and link the phenotypic trait with genomic data, based on Hi-C, ATAC, and RNA-seq data of specific tissues. We declared yellow pitaya as an autotetraploid with a 7.16 Gb genome size (harboring 27,246 high confidence genes) and majorly evolved from diploid ancestors, which remains unknown. Beyond generating the genome assembly, we explored the 3D chromatin organization which revealed insights into the genome, compartments A (648 and 519), compartments B (728 and 1064), topologically associated domains-TADs (3376 and 2031), and varying numbers of structural variations (SVs) in diploid and polyploid pitaya species, respectively. Overall, TAD boundaries were enriched with the motifs of AP2, WRKY18/60/75, MYB63/116, PHL2, and GATA8 in both pitaya species. By linking the open chromatin genomic structure to function, we identified the major changes in betalains biosynthesis pathway in diploid and polyploid pitaya. Moreover, the higher genetic expression of SmeADH1 [Chr11, Compartment A (135400000 - 135500000), genes inside the TAD region (135480000 - 135520000)], and lower expression of HuDOPA [Chr11, Compartment A (87100000 - 87200000), genes inside the TAD region (87160000-87200000)] acts as a key regulator of yellow and red color on the pericarp of polyploid and diploid pitaya, respectively. In addition, higher expression of HuCYP76AD1 genes in diploid pitaya and lower expression of SmeCYP76AD1 in polyploid pitaya potentially created the difference in the oxidase process that led to the production of betacyanin and betaxanthin, respectively. Furthermore, our results revealed not only the type of motifs that play a potential role in trait patterning but we also further uncovered that motif count in TAD-boundaries may impact the gene expression within the TAD regions of diploid and polyploid pitaya. Our valuable genomic resource and comparison of 3D euchromatin architecture of diploid and polyploid pitaya species will not only aid in the advancement of molecular breeding efforts but also offer insights into the organization of genomes, SVs, compartmentalization (A and B), and TADs, which have the potential to strengthen the idea of TADs-based trait improvement to achieve global food security.

plant biology↗
bioRxiv2024

Claudin-4 remodeling of nucleus-cell cycle crosstalk maintains ovarian tumor genome stability and drives resistance to genomic instability-inducing agents.

During cancer development, the interplay between the nucleus and the cell cycle leads to a state of genomic instability, often accompanied by observable morphological aberrations. These aberrations can be controlled by tumor cells to evade cell death, either by preventing or eliminating genomic instability. In epithelial ovarian cancer (EOC), overexpression of the multifunctional protein claudin-4 is a key contributor to therapy resistance through mechanisms associated with genomic instability. However, the molecular mechanisms underlying claudin-4 overexpression in EOC remain poorly understood. Here, we altered claudin-4 expression and employed a unique claudin-4 targeting peptide (CMP) to manipulate the function of claudin-4. We found that claudin-4 facilitates genome maintenance by linking the nuclear envelope and cytoskeleton dynamics with cell cycle progression. Claudin-4 caused nuclei constriction by excluding lamin B1 and promoting perinuclear F-actin accumulation, associated with remodeling nuclear architecture, thus altering nuclear envelope dynamics. Consequently, cell cycle modifications due to claudin-4 overexpression resulted in fewer cells entering the S-phase and reduced genomic instability. Importantly, disrupting biological interactions of claudin-4 using CMP and forskolin altered oxidative stress cellular response and increased the efficacy of PARP inhibitor treatment. Our data indicate that claudin-4 protects tumor genome integrity by remodeling the crosstalk between the nuclei and the cell cycle, leading to resistance to genomic instability formation and the effects of genomic instability-inducing agents. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/611120v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@7ed420org.highwire.dtl.DTLVardef@98949eorg.highwire.dtl.DTLVardef@1453a68org.highwire.dtl.DTLVardef@1fdab87_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Claudin-4 plays a crucial role in remodeling the cytoskeleton, particularly influencing nuclear architecture. This remodeling appears to act as a regulatory mechanism, limiting the progression of ovarian cancer cells into the S-phase and correlating with reduced genomic instability in ovarian tumors. Moreover, since olaparib treatment triggered a cellular oxidative response, it is likely that this claudin-4-mediated remodeling contributes to resistance against the effects of the PARP inhibitor. C_FIG

cancer biology↗
bioRxiv2024

Same strain, two genomes: Creating a consensus circular genome of Myxococcus xanthus DZ2 revealed the diversity of a large polyploid prophage region within the close-related myxobacterial strains

One of the well-known myxobacterial model organism, i.e., Myxococcus xanthus DZ2 strain has three reported assemblies of which two complete assemblies (MxDZ2_Tam and MxDZ2_Nan) have been reported in the last three years for the same strain procured from same culture collection stock. Raw assemblies of this same strain were reported circular and differed by 6.4 kb, raising questions about their accuracy. Therefore, our computational analysis, removing duplicate ends, aligning genomes to the origin of replication, and circularization, revealed a minimal size difference of only 32 bp, with MxDZ2_Tam being slightly larger. Further comparative analysis identified 40 sequence variations: 38 indels and 2 substitutions, with 24 variations concerning 18 coding genes. Eight of these 24 variations triggered frameshift mutations, seven of them encountered a premature stop codon followed by a second ORF and the remaining three had a premature stop codon followed by a non-coding region. 78% of these variations were detected in the regions which had repeated bases, especially guanine and cytosine, which is one of the well-known sequencing limitations. Although PacBio HiFi technology, used for the complete assemblies, boasts a low error rate, it remains higher than the 454-platform used for the earlier MxDZ2_Kirby assembly. Using MxDZ2_Kirby as a reference, we determined that most variations were specific to MxDZ2_Nan, while MxDZ2_Tam showed greater consistency with MxDZ2_Kirby. Based on these findings, we constructed a consensus truly circular genome for the same M. xanthus DZ2 strain. Additionally, we monitored divergence between M. xanthus DZ2 and its close relative M. xanthus DK1622 in the number of Mx-alpha regions, which are linked to interspecies and intraspecies antagonism via the toxin gene sitA. Further comparative genome analysis across 61 myxobacteria revealed the presence of Mx-alpha regions in five other organisms, though only M. xanthus DZ2 and DZF1 contained all three Mx-alpha regions. Overall, this study underscores the need for meticulous validation of sequencing-based genome assemblies and their variations along with highlighting the genomic diversity within M. xanthus strains based on a large polyploid prophage region, known as Mx-alpha. ImportanceSequencing an organism is an efficient way to investigate its physiology and function. Through this study, we focused on resolving differences between two genome assemblies of the same strain, i.e., M. xanthus DZ2, procured from the same culture collection and assembled via two different organisations. We identified 40 differences between these two, which led to inconsistencies in how some proteins were predicted and annotated. By comparing these assemblies with a third draft genome, we created a more accurate and reliable consensus truly circular genome for this strain. We also investigated a particular region of the genome, known as Mx Alpha, that contains genes for toxin-antitoxin systems, which play a role in helping the bacteria recognize and interact with related strains. These findings provide new insights into the diversity of this region in Myxococcus and its phylum Myxococcota relatives, shedding light on how these bacteria interact within their communities.

bioinformatics↗
bioRxiv2025

An improved gray whale assembly highlights how allospecific reference-genome choice can affect genomic diversity estimates

Gray whales (Eschrichtius robustus) are unique as bottom feeding baleen whales and they have long been a conservation concern on both sides of the Pacific, in part because they migrate and disperse farther than any other species on earth. They experienced drastic population size declines due to environmental changes and commercial whaling. Here, we present an improved genome assembly for the gray whale. This genome assembly covers 2.4 Gb divided across 2689 contigs with an N50 of 15Mb. From the new assembly, we identify 75Mb sex-linked contigs and a identify 94.6% of searched genes based on Benchmarking Universal Single-Copy Ortholog score. We use the gray whale assembly to explore the effects of mapping to conspecific vs allospecific reference genomes when estimating genome-wide heterozygosity (H) and runs of homozygosity (ROH). The use of allospecific genomes significantly underestimate both H and ROH burden regardless of genomic distance and assembly quality. Our analyses highlight the importance of using contiguous conspecific assemblies in whale genomics and conservation. SignificanceGray whales are unique in their behavior, morphology and ecology. The novel and contiguous genome assembly presented here will serve as a valuable resource for studies of their population and comparative genomics, as well as for identifying key adaptations that have evolved in this clade. Finally, our results demonstrate that biases can arise when using allopatric assemblies to evaluate diversity metrics, so they should be used and interpreted with caution.

evolutionary biology↗
bioRxiv2025

Characterization of nuclear genome size and variation in a freshwater snail model system featuring a recent whole-genome duplication

Species are defined by unique nuclear genome characteristics like nucleotide composition, genomic structure, and genome size. These fundamental aspects of the nuclear genome can themselves be the object of natural selection. We here provide the first high-quality direct measurements of nuclear genome DNA content in a representative diverse sample of Potamopyrgus antipodarum, an Aotearoa New Zealand freshwater snail that is a textbook example of the maintenance of sexual reproduction in nature and is invasive worldwide. We used propidium-iodide-based flow cytometry to characterize nuclear DNA content, and its variation, in nearly 100 P. antipodarum from multiple populations representing both sexual and asexual individuals. We also estimated nuclear DNA content in multiple P. estuarinus, a closely related obligately sexual species. These data confirmed and extended earlier lines of evidence for polyploidy and variable genome size within asexual P. antipodarum and provided the first direct evidence for distinctly higher nuclear genome content in diploid (sexual) P. antipodarum relative to diploid sexual P. estuarinus. These data are consistent with genomic evidence for a recent whole-genome duplication (WGD) and subsequent and in-process rediploidization in P. antipodarum, setting the stage for use of Potamopyrgus as a model for WGD and its consequences.

evolutionary biology↗
bioRxiv2025

FetchM: Streamlining Genome and Metadata Integration for Microbial Comparative Genomics

FetchM is a Python-based tool for fetching, analyzing, and combining bacterial genomic metadata from the NCBI Genome database and associated sample metadata from NCBI BioSample records. When working with bulk-genome analyses, such as comparative genomics or pangenome studies, you often require a unified dataset that captures the full context of a particular bacterial species population. You can obtain genomic metadata by downloading the ncbi_dataset.tsv file from the NCBI Genome database for a specific bacterial species. However, this file lacks key metadata fields such as Collection Date, Host, Geographic Location, and Isolation Source. FetchM fills this gap by automatically retrieving these missing fields, linking genome accessions to their corresponding BioSample records via the NCBI Entrez API. FetchM not only helps you compile a complete, metadata-rich dataset but also provides visualizations and summaries of both genomic and contextual metadata features. You can filter and download sequences based on specific criteria such as year, host, isolation source, country, continent, and subcontinent, making it a flexible and powerful companion for large-scale genomic studies. FetchM is available as an open-source tool at: https://github.com/Tasnimul-Arabi-Anik/FetchM. It can also be downloaded as a PyPI package.

bioinformatics↗
bioRxiv2025

Population genomic scan of endogenous retrovirus insertions revealed cryptic drivers of selective sweep in wild house mouse genomes

Endogenous retroviruses (ERVs) represent a major source of structural variation in mammalian genomes, yet their diversity in wild populations remains poorly understood. Here, we conduct a comprehensive genome-wide survey of non-reference ERV insertions in wild house mice (Mus musculus) to characterize their distribution and evolutionary dynamics. Using a newly developed bioinformatics pipeline, we detected and annotated over 100,000 non-reference ERV insertions from short-read sequencing data across 163 wild mouse genomes. Our analyses revealed marked differences in ERV insertion patterns among subspecies and populations, including variation in genomic localization and population-specific polymorphisms. These heterogeneous patterns suggest distinct evolutionary histories and host-retrovirus interactions across populations. For instance, we describe the distribution of the ERV-derived Fv4 locus, which shows subspecies-restricted occurrence and confers resistance to murine leukemia viruses (MLVs). Several lines of evidence showed that the spread of Fv4 insertions in Korean population has been driven by adaptive introgression from neighboring populations. Our study provides the first large-scale population genomic scan of ERV diversity in wild house mice. By cataloguing extensive polymorphism in non-reference ERV insertions, our results highlight the role of ERVs as dynamic genomic elements that contribute to structural variation and adaptive evolution. Article SummaryEndogenous retroviruses (ERVs) are viral sequences embedded in animal genomes that can create structural genetic variation. In this study, we conducted a genome-wide survey of non-reference ERV insertions in 163 wild house mice using short-read sequencing data and a newly developed computational pipeline. We identified more than 100,000 polymorphic ERV insertions and found substantial differences among subspecies and geographic populations. One example, the ERV-derived Fv4 locus, illustrates how ERV variation can influence the genetic pattern of polymorphisms in the species. These results demonstrate that ERVs are dynamic genomic elements that contribute to population divergence and adaptive evolution.

evolutionary biology↗
bioRxiv2026

Genome-wide discovery of cis-regulatory elements in a large genome

Identifying non-coding regulatory elements in the genome poses a challenge in most organisms. Classical methods rely on trial and error to test the regulatory activities of DNA fragments using reporter constructs. In large eukaryotic genomes, where cis-regulatory elements can spread over long distances, separated by large stretches of non-functional DNA, this trial and error approach is particularly challenging. Here, we generate two types of resources that can be used to narrow the search for such cis-regulatory elements in the 3.6 Gbp genome of Parhyale hawaiensis (comparable in size to the human genome). First, we use bulk ATAC-seq to uncover genome-wide patterns of chromatin accessibility in embryonic and adult tissues of Parhyale (whole embryos and legs), and single-nucleus ATAC-seq to identify regions of open chromatin in diverse cell types recovered from adult legs, including epidermal, neuronal, muscle and blood cells. Second, by sequencing the genomes of three congeneric species of Parhyale hawaiensis - P. darvishi, P. aquilina and P. plumicornis - we identify islands of sequence conservation across the genome, corresponding to DNA elements that are functionally constrained during evolution. We present an approach by which low-coverage (10-15x) short-read genome sequencing, without genome assembly, is sufficient to provide reliable maps of sequence conservation. This approach cuts the cost and labour required to generate these maps, making the identification of cis-regulatory elements more widely accessible. We demonstrate the utility of these resources by identifying cis-regulatory elements that drive robust expression of fluorescent reporters ubiquitously and in specific cell types.

developmental biology↗
bioRxiv2026

Chromosome-scale genome assembly of diploid halophyte Thinopyrum bessarabicum excludes J genome from polyploid Thinopyrum ancestry

Wild relatives of wheat harbour genetic diversity essential for improving resilience to climate-driven stresses, yet their deployment is hampered by unresolved evolutionary relationships and the absence of reference genomes. Here we present a chromosome-scale reference genome for Thinopyrum bessarabicum, a diploid halophyte and high-priority donor for wheat salt tolerance breeding. A key unresolved question is whether the diploid J genome contributed directly to the subgenome composition of extant polyploid Thinopyrum species, and which genomic features underpin its exceptional salt tolerance. Using this resource, we show that the diploid J genome of Th. bessarabicum is not represented among the subgenomes of polyploid Thinopyrum species, resolving a long-standing ambiguity in Triticeae genomics. Gene-level resolution of the reciprocal 4/5 chromosomal translocation across six related Triticeae species identifies conserved breakpoint gene pairs, supporting a single ancestral rearrangement. Genome-wide gene content analysis shows that halophytic capacity is underpinned by quantitative expansion of conserved stress-response gene families. Salt tolerance phenotyping validates chromosome 5J as a tolerance locus in both Th. bessarabicum and wheat introgression lines. A physically anchored marker framework and dual-reference skim-sequencing pipeline enable precise megabase-resolution characterisation of Th. bessarabicum introgressions in wheat, providing a genomic foundation for deploying J-genome diversity in crop improvement.

plant biology↗
bioRxiv2026

Independent evolutionary trajectories of genomic repeats and non-repeat genome features in Actinomycetota

Genomic repeats, particularly simple sequence repeats, influence genome stability and gene regulation. While many genomic traits exhibit phylogenetic signal and pulsed evolution, repeat elements have rarely been examined in a comparative framework, and their evolutionary relationships with other genome features remain poorly understood. We contrasted the trait evolution of genomic repeats with non-repeat traits across diverse actinobacterial orders, testing for phylogenetic signal, evolutionary mode, and pulsed dynamics using time-calibrated, 16S rRNA, and whole-genome sequence (WGS) trees. Non-repeat traits consistently exhibited signs of punctuated evolution, with larger pulses in species-rich orders such as Mycobacteriales and Actinomycetales; repeats, by contrast, were evolutionarily labile, lacking phylogenetic signal and largely decoupled from other genomic traits. Bifidobacteriales was the sole exception, with repeats exhibiting phylogenetic signal only under the WGS tree. The WGS tree also recovered a stronger signal for genome-level traits, highlighting its utility in comparative analyses. Genome size evolution in Actinomycetota appears driven primarily by protein-coding gene expansion rather than repeat accumulation.

evolutionary biology↗
bioRxiv2026

Genomic foundation model embeddings encode higher-order viral genome architecture beyond sequence composition: a benchmark of Evo 2

Genomic foundation models such as Evo 2 are increasingly applied to microbial genomics, yet how well their representations capture viral genome organisation, and how reliably they generate viral sequence, remain poorly characterised. We present a reproducible benchmark of Evo 2 on viral genomes. Using a pre-registered RefSeq viral corpus (19,429 genomes, organised by Baltimore class and host domain), we evaluated three axes: linear probes decoding Baltimore class, host domain and viral family from mean-pooled embeddings; ridge-regression probes recovering genomic features, including higher-order architectural properties such as gene density, coding fraction and gene overlap; and generative completion of fragmented genomes, scored on a leakage-safe set of eukaryote-infecting viruses (excluded from Evo 2s training corpus by design) against a bacteriophage comparator. All probes used cross-validation with sequence-identity-clustered folds, benchmarked against both a GC-and-length control and a 6-mer composition representation. From its optimal intermediate layer, the 20B embedding classified Baltimore class at 0.96 accuracy and host domain at 0.99, exceeding both baselines; for viral family, however, 6-mer composition (0.89) matched the embedding (0.91. Most informatively, the embedding decoded coding fraction, gene density and gene overlap (R{superscript 2} = 0.61, 0.77 and 0.64) far beyond 6-mer composition (0.10, 0.38 and 0.27), evidencing genuine encoding of genome architecture rather than nucleotide composition (p < 0.001). Performance scaled with model size. In generation, perplexity was lower for bacteriophages (1.18 bits/nt) than for held-out eukaryotic viruses (1.80). Evo 2 encodes functional viral genome architecture beyond composition, while taxonomic and generative behaviour partly reflect composition and training exposure.

bioinformatics↗
bioRxiv2026

SAR11 Genome Atlas: a genome and gene catalog for functional profiling of the most abundant bacterial clade in the ocean

The SAR11 clade, also known as the order Candidatus Pelagibacterales, is among the most abundant bacterial lineages in the ocean and plays central roles in marine biogeochemical cycles. However, many SAR11 genes remain functionally uncharacterized, highlighting the need for a comprehensive, integrated catalog that supports genomic, functional, and ecological analyses across the clade. Here, we present the SAR11 Genome Atlas, an interactive ortholog group (OG)-centered web resource that integrates 542 SAR11 genomes, including all 132 cultured strain genomes, with functional annotations, synteny, phylogenetic distribution, metatranscriptomic expression, and predicted protein structure information. To demonstrate its utility, we used environmental expression profiles to identify OGs associated with high-latitude environments, recovering OGs known to be involved in cold adaptation and proposing a hypothesis for the function of uncharacterized protein. We further analyzed phylogenetic distribution patterns to identify mutually exclusive functional modules, including candidate alternative systems for Mn/Zn homeostasis and phosphate acquisition, and to associate these modules with distinct oceanographic environments. Together, these case studies demonstrate that the SAR11 Genome Atlas supports complementary analyses that connect environmental signals to genes of interest and use phylogenetic or functional distributions to generate hypotheses about ecological specialization. Through a user-friendly web interface, the SAR11 Genome Atlas enables researchers to explore genomic, environmental, and structural information without specialized computational expertise. All data and analysis outputs are freely accessible online at [https://stsnsn.github.io/SAR11_Atlas/]. The SAR11 Genome Atlas thus provides a scalable framework for generating and testing hypotheses that connect SAR11 genomic variation to protein function and oceanographic context, supporting advances in marine microbial ecology and biogeochemistry.

microbiology↗
bioRxiv2018

Identification of meiotic recombination through gamete genome reconstruction using whole genome linked-reads

Meiotic recombination (MR), which transmits exchanged genetic materials between homologous chromosomes to offspring, plays a crucial role in shaping genomic diversity in eukaryotic organisms. In humans, thousands of meiotic recombination hotspots have been mapped by population genetics approaches. However, direct identification of MR events for individuals is still challenging due to the difficulty in resolving the haplotypes of homologous chromosomes and reconstructing the gamete genome. Whole genome linked-read sequencing (lrWGS) can generate haplotype sequences of mega-base pairs (N50 ~2.5Mb) after computational phasing. However, the haplotype information is still isolated in a large number of fragmented genomic regions and limited by switch errors, impeding its further application in the chromosome-scale analysis. In this study, we developed a tool MRLR (Meiotic Recombination identification by Linked-Read sequencing) for the analysis of individual MR events. By leveraging trio pedigree information with lrWGS haplotypes, our pipeline is sufficient to reconstruct the whole human gamete genome with 99.8% haplotyping accuracy. By analyzing the haplotype exchange between homologous chromosomes, MRLR identified 462 high-resolution MR events in 6 human trio samples from the Genome In A Bottle (GIAB) and the Human Genome Structural Variation Consortium (HGSVC). In three datasets of the HGSVC, our results recapitulated 149 (92%) previously identified high-confident MR events and discovered 85 novel events. About half (40) of the new events are supported by single-cell template strand sequencing (Strand-seq) results. We found that 332 (71.9%) MR events co-localize with recombination hotspots (>10 cM/Mb) in human populations, and MR breakpoint regions are enriched in PRDM9 and DMC1 binding sites. In addition, 48% (221) breakpoint regions were detected inside a gene, indicating these MRs can directly affect the haplotype diversity of genic regions. Taken together, our approach provides new opportunities in the haplotype-based genomic analysis of individual meiotic recombination. The MRLR software is implemented in Perl and is freely available at https://github.com/ChongLab/MRLR.

genomics↗
bioRxiv2016

Ethnically relevant consensus Korean reference genome towards personal reference genomes

Human genomes are routinely compared against a universal reference. However, this strategy could miss population-specific or personal genomic variations, which may be detected more efficiently using an ethnically-relevant and/or a personal reference. Here we report a hybrid assembly of Korean reference (KOREF) as a pilot case for constructing personal and ethnic references by combining sequencing and mapping methods. KOREF is also the first consensus variome reference, providing information on millions of variants from additional ethnically homogeneous personal genomes. We found that this ethnically-relevant consensus reference was beneficial for efficiently detecting variants. Systematic comparison of KOREF with previously established human assemblies showed the importance of assembly quality, suggesting the necessity of using new technologies to comprehensively map ethnic and personal genomic structure variations. In the era of large-scale population genome projects, the leveraging of ethnicity-specific genome assemblies as well as the human reference genome will accelerate mapping all human genome diversity.

Genomics↗
bioRxiv2016

An improved assembly and annotation of the allohexaploid wheat genome identifies complete families of agronomic genes and provides genomic evidence for chromosomal translocations.

Advances in genome sequencing and assembly technologies are generating many high quality genome sequences, but assemblies of large, repeat-rich polyploid genomes, such as that of bread wheat, remain fragmented and incomplete. We have generated a new wheat whole-genome shotgun sequence assembly using a combination of optimised data types and an assembly algorithm designed to deal with large and complex genomes. The new assembly represents more than 78% of the genome with a scaffold N50 of 88.8kbp that has a high fidelity to the input data. Our new annotation combines strand-specific Illumina RNAseq and PacBio full-length cDNAs to identify 104,091 high confidence protein-coding genes and 10,156 non-coding RNA genes. We confirmed three known and identified one novel genome rearrangements. Our approach enables the rapid and scalable assembly of wheat genomes, the identification of structural variants, and the definition of complete gene models, all powerful resources for trait analysis and breeding of this key global crop. [Supplemental material is available for this article.]

genomics↗