Biology subjects

Itoh, T.

Publications and source records attributed to Itoh, T..

At least 19 recordsLinked to original sources

bioRxiv2026

Genomic, spatial, and evolutionary insights into a dominant Mycoplasmatota symbiont colonizing the body wall of deep-sea holothurians

Subcuticular bacteria (SCB) are widespread symbionts of echinoderms and often dominate the body-wall microbiome, suggesting important roles in host physiology. However, their diversity, metabolic properties, and host associations remain poorly characterized. Here, we report a novel dominant SCB lineage associated with deep-sea holothurians, Scotoplanes spp. collected from the Northwest Pacific. We recovered two high-quality genomes, including a 649-kb complete circular genome, and propose a new genus and species, "Candidatus Abyssoplasma scotoplanesicola", within Mycoplasmatota. The two genomes showed a highly reduced metabolic repertoire, lacking central pathways including glycolysis. In contrast, acidic cell-surface-associated proteins, including large proteins exceeding 5,000 amino acids, accounted for 27.6% of the complete genome and clustered near defense islands. Localized genome plasticity in these regions, revealed by comparison between the two closely related genomes, suggests a possible mechanism for diversification of cell-surface proteins at the host-symbiont interface. "Candidatus Abyssoplasma scotoplanesicola" occupied 76.4-98.9% of the body-wall microbiome of the Scotoplanes specimens. Fluorescence in situ hybridization analysis confirmed that these bacteria formed aggregates on the epidermal side of the body wall. Overall, this study provides genome-and spatially resolved views of dominant SCB in holothurians and offers evolutionary insights into host-interface diversification in the deep-sea holothurian body wall.

microbiology↗

bioRxiv2026

Mutation-agnostic gene insertion therapy for RHO-associated autosomal dominant retinitis pigmentosa using zinc finger nucleases

PurposeAutosomal dominant retinitis pigmentosa caused by mutations in the rhodopsin gene (RHO-adRP) is among the most prevalent inherited retinal dystrophies. With nearly 100 distinct pathogenic variants identified to date, the mutational heterogeneity of RHO-adRP severely limits the clinical utility of mutation-specific therapeutic strategies. We aimed to develop a mutation-agnostic gene insertion therapy using homology-independent targeted integration (HITI) mediated by zinc finger nuclease ZF-ND1 targeting the human RHO 5'-UTR, and to validate its preclinical efficacy, safety, proof-of-concept, and proof-of-mechanism. MethodsWe developed two AAV serotype 5 (AAV5) vectors: one encoding the ZF-ND1 pair (AAV5-ZFN) and one carrying the therapeutic donor cassette (AAV5-RHO), delivered by subretinal co-injection. ZF pairs targeting the RHO 5'-UTR were arranged and refined by in vitro validation; AAV vector optimization and mechanistic verification were performed in human induced pluripotent stem cell (hiPSC)-derived retinal organoids-derived retinal organoids; longitudinal proof-of-concept efficacy and safety were assessed in a humanized RHO-T17M rat disease model by 6-month optical coherence tomography (OCT); and proof-of-mechanism was evaluated in non-human primate retina. ResultsWe identified a ZF-ND1 pair achieving cleavage efficiency comparable to the SpCas9 RNP previously validated for HITI-mediated editing in mouse retina, and optimized the ZF array composition and NLS configuration for efficient editing especially in post-mitotic photoreceptors. HITI-mediated donor integration was confirmed across multiple cell types and ZFN:donor ratios. In the humanized rat disease model, the therapeutic vector provided outer nuclear layer (ONL) preservation by 6 months, with AAV5-ZFN:AAV5-RHO ratios of 1:1 and 1:2 maintaining ONL thickness above the preservation threshold. In the non-human primate retina, the fraction of HITI-edited rod photoreceptors exceeded the 20% therapeutic correction threshold in the successfully treated individual. ConclusionsThese findings support the advancement of this therapeutic vector to first-in-human trials as a mutation-agnostic insertion therapy applicable to all patients with RHO-adRP, irrespective of the specific causative variant.

genetics↗

bioRxiv2026

DPP9-mediated inflammasome repression protects against checkpoint inhibitor lung toxicity

Over one million patients receive cancer immunotherapy annually, yet the mechanisms underlying life-threatening immune-mediated toxicities remain poorly understood. Checkpoint inhibitor pneumonitis (CIP) is the leading cause of immunotherapy-related mortality, with a case fatality rate approaching 10%, and no genetic risk factors have been described to date. We identified Dipeptidyl-peptidase 9 (DPP9) as the first genetic susceptibility gene for CIP in a clinico-genomics cohort of 4,397 patients treated with immune checkpoint inhibitors. Mechanistically, DPP9 suppresses CARD8 inflammasome activation and IL-18 secretion in human monocytes, a pathway which is engaged prior to CIP onset, with IL-18 selectively elevated in the plasma of patients who subsequently develop CIP. Myeloid-restricted ablation of Dpp8 and Dpp9 in mice recapitulated the pulmonary histopathological and immunological hallmarks of CIP, including granuloma formation, accumulation of IFN{gamma}-producing T cells and monocyte-derived macrophages. Each of these phenotypes were driven by excessive IL-18 secretion. Together, these findings establish DPP9 as a genetic determinant of CIP and nominate IL-18 blockade as a mechanistically rational therapeutic strategy.

immunology↗

bioRxiv2026

An evolutionary landscape of sesame: chromosomal variation, allopolyploid speciation and metabolic specialization.

Sesame (Sesamum indicum) is one of the earliest domesticated oilseed crops and is valued for antioxidant lignans that stabilize oil quality. However, the genomic and evolutionary history of the genus Sesamum, including the origin of its allotetraploid relative S. radiatum and the diversification of lignan metabolism, remains poorly understood owing to limited chromosome-scale genomic resources. Here we present chromosome-level genome assemblies for three wild Sesamum species, two Ceratotheca species and a Japanese sesame cultivar to reconstruct genome and karyotype evolution across the Sesamum-Ceratotheca complex. Comparative analyses show that the derived x=16 lineage originated from an ancestral x=13 karyotype through chromosome fission, fusion and translocation, whereas another x=13 lineage underwent extensive restructuring associated with retrotransposon expansion. Phylogenomics places Ceratotheca within the x=16 Sesamum clade and reveals that S. radiatum originated through hybridization involving a C. sesamoides-like ancestor. The antioxidative lignan gene CYP92B14 was reintroduced via the BB progenitor, linking hybridization with restoration of oil-stabilizing metabolism during sesame evolution.

genomics↗

bioRxiv2026

An APP-centered molecular gateway integrates innate immunity and retinoic acid signaling to drive irreversible metamorphic commitment

The mechanisms by which environmental signals induce permanent developmental changes remain a fundamental biological problem. We investigated sea star metamorphosis, where microbial biofilms induce a total body plan reorganization. Using systems biology and functional assays, we identified a three-tiered signaling cascade: sensing, conversion, and execution. The immune adaptor MyD88 senses microbes, while MAPK proteins convert this signal into a retinoic acid developmental cue. An amyloid precursor protein (APP)-centered module acts as the irrevocable commitment gateway, stabilized by a positive feedback loop to ensure irreversibility. Remarkably, the genes driving this transition overlap with human pathways for Alzheimers disease and ADHD/Autism. By defining this ancient neuro-immune axis in an echinoderm adult body plan similar to the chordate head, our study establishes sea star metamorphosis as a model for understanding the evolutionary origins of human neurological disorders from the evolutionary developmental pathology perspective.

developmental biology↗

bioRxiv2026

Rice Annotation Project Database (RAP-DB): literature-curated gene annotation and integrated omics resources for rice functional genomics and molecular breeding

High-throughput sequencing technologies have enabled the generation of high-quality reference genomes for numerous rice cultivars. However, inferring gene functions, associated phenotypes, and causal variants from these sequences remains challenging. The Rice Annotation Project Database (RAP-DB; https://rapdb.dna.affrc.go.jp) is a curated genomic resource that provides comprehensive gene annotations for the reference genome of Oryza sativa ssp. japonica cv. Nipponbare. Since its major update in 2013, gene models and functional annotations have been continuously revised through expert manual curation of newly published literature related to rice genes. As of March 2025, a total of 6,631 transcripts corresponding to 6,371 loci have been curated based on 4,699 peer-reviewed publications. These curated genes are functionally characterized and are frequently associated with agronomic traits, including yield components, stress tolerance, and disease resistance. To support molecular breeding, RAP-DB now provides a curated catalogue of 904 agronomically important loci, including gene symbols, functional descriptions, and associated traits, together with more than 1,000 functionally characterized alleles compiled from the literature. In addition to in-house expert curation, RAP-DB integrates community-curated datasets for major gene families, such as WRKY transcription factors, S-domain receptor-like kinases, and leucine-rich repeat-containing receptors, thereby expanding coverage of key regulatory and defense-related genes. RAP-DB also incorporates reanalyzed RNA sequencing expression profiles alongside microarray-based expression data and co-expression networks, offering gene-centric views of expression patterns across tissues, conditions, and developmental stages. Furthermore, RAP-DB is linked to genome-wide variation datasets from diverse rice varieties through the TASUKE+ genome browser, enabling exploration of allelic diversity across varieties. To enhance annotation quality and long-term sustainability, AI-assisted literature screening and a web-based feedback system have been introduced, allowing users to submit corrections to gene models and report newly characterized genes or relevant publications. Together, these developments strengthen RAP-DB as a primary, literature-based gene annotation resource and provide a practical foundation for molecular breeding in rice.

bioinformatics↗

bioRxiv2025

Chloroplast- and Mitochondrion-Specific Random C-to-T Mutagenesis for Forward Genetics of Organelle Genomes

Organelle genomes in plastids (including chloroplasts) and mitochondria encode essential genes for photosynthesis, respiration, and agronomic traits, representing promising targets for crop improvement. However, their high copy number and non-Mendelian inheritance have long hindered efficient modification compared to nuclear genomes. Recent advances in organelle base editing (C-to-T and A-to-G) have enabled precise nucleotide substitutions, yet information on useful mutations remains limited. Here, to establish a forward genetics platform for C-to-T substitutions, we developed a method to introduce random C-to-T mutations throughout the entire organelle genomes of Arabidopsis thaliana. We engineered a fusion protein, WHY2-CD mutator, combining cytidine deaminase (CD), uracil glycosylase inhibitor, and sequence-nonspecific DNA-binding protein WHIRLY2 (WHY2), fused to organelle-targeting peptides. This system introduced dispersed C-to-T substitutions specifically within plastid or mitochondrial genomes. In T2 lines, we identified homoplasmic (homozygous) plastid genome mutants, including rpoA knockouts and rbcL variants with an amino acid substitution. Screening T3 populations on spectinomycin revealed plastid genome mutants with resistant traits and their causal mutation. These mutations can be transferred or combined using targeted base editors, such as transcription activator-like effector cytidine deaminase (TALECD). This comprehensive, C-to-T-focused mutagenesis provides a powerful tool for organelle forward genetics and molecular breeding.

plant biology↗

bioRxiv2025

Chromosome-scale Genome Assemblies of Two Allopolyploid Cuscuta Species Uncover Genomic Signatures of Parasitic Lifestyle and Polyploid Evolution

Dodders (Cuscuta spp.) is an obligated parasitic plant, which lost a large part of photosynthetic genes but gained host genes through parasitism-mediated horizontal gene transfer (HGT). Their migratory ecology across the world would contribute to complexity of the speciation via geographic isolation. Here we report the de novo genome assemblies of the two phylogenetically distinct dodders; C. chinensis (2n=4x=60) and C. campestris (2n=4x=60) that are classified into Clade B and Clade H of subgenus Grammica, respectively. Relatively low completeness of BUSCO genes ca.87% indicated progressive gene loss after evolution of parasitic lifestyle due to release from functional constraints as photosynthesis and organ development. Comparative genomics uncovered that both species are the genome size is completely different regardless of the same cytotypes and allopolyploid through the independent ancient hybridization between different parents. Various genomic rearrangements including 1) gene gain and loss events, 2) homoeologous recombination between two subgenomes and 3) the lineage-specific proliferation of transposable elements likely contribute to their genomic diversity and sexual isolation of the two lineages partly sharing their habitats. Our findings not only provide genomic basis to survey parental species for allopolyploidization but also help to understand unique speciation of parasitic dodders through these chromosomal natures.

genomics↗

bioRxiv2025

Whole-genome sequencing of diverse 351 cultured prokaryotes including yet-unsequenced fastidious type strains

Genome sequences provide fundamental information for both basic and applied life sciences. Whole-genome sequencing is now requested for describing novel prokaryotic species and designating their type strains, which serve as representative and well-characterized strains of the species. Indeed, the number of sequenced prokaryotic genomes has been rapidly increasing. However, a considerable number of isolated strains, particularly "fastidious" type strains such as strict anaerobes and slow growers, remain without genome sequence information. Here we report the whole-genome sequencing of 290 bacterial and 61 archaeal strains, including fastidious type strains, obtained from Japan Collection of Microorganisms (JCM) using a combination of short- and long-read sequencing technologies. The dataset includes 284 type strain genomes and 235 complete genomes. Notably, in the dataset, genomes of over 200 strains, including over 150 type strains, had not been made publicly available. Comparative genomic analysis suggests that some strains need to be assigned to novel taxa or reclassified. Functional gene survey indicates that some strains possess previously unrecognized potential for carbon fixation or bioactive secondary metabolite production. Our dataset will contribute to more accurate taxonomic classification, fill gaps in the phylogeny of prokaryotes, and provide insights into their physiology and ecology.

microbiology↗

bioRxiv2025

Genome assembly and annotation of the naked mole rat Heterocephalus glaber reared in Japan

The naked mole rat (NMR, Heterocephalus glaber) is a eusocial rodent that is native to northeastern Africa. NMRs exhibit extraordinary traits such as longevity, resistance to age-related decline, and remarkable hypoxia tolerance. Although the reference genome of this species has been determined because of its unique characteristics, the significance or role of intraspecific genomic variations remains unknown. In this study, we used PacBio long-read sequencing to generate a genome assembly of NMR reared in Japan. The assembled genome is 2.56 Gb. Benchmarking Universal Single-Copy Orthologs (BUSCO) revealed high completeness (95.2%). BRAKER3 estimated 26,714 protein-coding genes, and we successfully added functional annotations for 26,232 protein-coding genes using the functional annotation workflow. We identified 417 gene models that were previously undetectable in the reference genome of this species. We also identified structural and amino acid sequence variations between our assembly and the reference genome, suggesting the presence of intraspecific genomic variations. This new genomic resource could help uncover the molecular mechanisms underlying the behavioral and physiological traits of NMR.

genomics↗

bioRxiv2025

Inverse signal importance in real exposome: How do biological systems dynamically prioritize multiple environmental signals?

Living organisms integrate multiple signals from their exposome, the totality of environmental influences experienced throughout life, to adapt to complex, non-stationary environments. While organisms are thought to flexibly prioritize relevant signals depending on context, its regulatory mechanisms remain largely unknown. Laboratory studies with precisely controlled conditions fail to capture this adaptability by isolating organisms from the complex exposome. Here, we developed a machine learning framework, Inverse Signal Importance (ISI), to infer how organisms prioritize external signals from time-series data of environmental factors and physiological responses. We applied ISI to analyze gonadal development in medaka fish under natural outdoor conditions, tracking gonadosomatic index alongside environmental signals including water temperature, day length, and solar radiation over two years. Our analysis revealed that signal importance levels exhibit complex dynamics distinct from simple environmental periodicity and correlates significantly with specific gene expression patterns. Notably, genes associated with temperature-related signal importance display differential expression between outdoor and controlled laboratory conditions, suggesting their role in environmental adaptation. These findings indicate that ISI effectively captures latent physiological dynamics in adaptation of exposome. By decomposing biological responses into deterministic and adaptive components, ISI provides a novel approach to uncover mechanisms of organismal adaptation in natural environments.

bioinformatics↗

bioRxiv2024

Evolution and functioning of an X-A balance sex determination system in hops

Chromosomal sex determining systems with male heterogamety include actively male-determining-Y and X-A balance systems, both of which are found in animals and plants. The sex-determining genes have been identified in several active-Y plant systems, but the evolution and functioning of X-A balance systems remains mysterious. To study this, we sequenced and compared the genomes of two hop species. The evolution of the hop X-A balance system involved an ancient recombination suppression event across a large X chromosome region shared by both species. In one species, an autosome fused to this ancestral sex chromosome, and recombination was subsequently suppressed again. The two evolutionary strata created in this neo-X have degenerated to different degrees, and evolved correspondingly different dosage compensation levels that correlate with histone modification patterns. Finally, we identified an X-specific ETR1-like ethylene receptor in the ancestral X region. Its dosage may affect sex determination, as part of the counting mechanism of this X-A balance system. One sentence summaryBased on whole genome sequences of the cultivated hop, Humulus lupulus, and its wild relative H. japonicus, we describe the evolution of sex chromosomal regions, three of which that evolved region-specific dosage compensation, and identify a candidate gene involved in their X-A balance sex determining system.

evolutionary biology↗

bioRxiv2024

Centromeric repeat diversity underlies non-Mendelian segregation pattern in hop (Humulus lupulus)

Aberrant meiosis in plants often leads to aneuploidy, genetic instability, and sterility. This can occur due to several factors, including chromosome misalignment, defective synapsis or environmental factors that may result in unusual genetic combinations in the offsprings. Unusual chromosome behavior during male meiosis in Humulus lupulus is linked to irregular chromosome segregation and genome instability. However, the origin of meiotic instability remains unclear. We analyzed the centromeric landscape of H. lupulus to determine its role in aberrant chromosomal segregation during cell division. Using a combination of bioinformatic, molecular and cytogenetic approaches, we identified new centromeric repeats and revealed two types of centromeric organizations. Cytogenetic localization on metaphase chromosomes confirmed the genomic distribution of major repeat arrays and revealed unique features that contribute to aberrant segregation. Two centromeric types are composed of the major repeats SaazCEN and SaazCRM1 which are further accompanied by chromosome-specific centromeric satellites, Saaz40, Saaz293, Saaz85, and HuluTR120. Chromosome 2 displays unbalanced segregation during the cell division, implicating an important role for its centromere structure in segregation patterns. Moreover, Saaz293 is a new marker for studying aneuploidy in hop. Our findings provide new insights on chromosome segregation in hop and highlight the diversity and complexity of the centromere organization in H. lupulus.

plant biology↗

bioRxiv2024

Structural insight into the nuclear transportation mechanism of PPARg by Transportin-1

The spatial and temporal control of protein is essential for normal cellular function. Proteins working in the nucleus have nuclear localization signal (NLS) sequences and are escorted into the nucleus by cognate nuclear transport receptors. A wealth of experimental data about NLS has been accumulated, and nuclear transportation mechanisms are established at the biochemical and structural levels. The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that control various biological responses. We recently reported that the transportation of PPAR{gamma} is mediated by Transportin-1, but PPAR{gamma} lacks a typical NLS sequence recognized by Transportin-1. Moreover, the recognition mechanism remains largely unknown. In this study, we determined the Cryo-EM structure of PPAR{gamma} in complex with Transportin-1 and revealed that Transportin-1 gripped the folded DNA binding domain and the Hinge region of PPAR{gamma}, indicating that PPAR{gamma} recognizes a folded domain with an extended region as a nuclear localization signal, not a canonical unstructured signal sequence, confirmed by the mutation analyses in vitro and in cultured cells. Our study is the first snapshot structure working in nuclear transportation, not in transcription, of PPAR{gamma}.

molecular biology↗

bioRxiv2023

Genome sequence and cell biological toolbox of the highly regenerative, coenocytic green feather alga Bryopsis

Green feather algae (Bryopsidales) undergo a unique life cycle in which a single cell repeatedly executes nuclear division without cytokinesis, resulting in the development of a thallus (> 100 mm) with characteristic morphology called coenocyte. Bryopsis is a representative coenocytic alga that has exceptionally high regeneration ability: extruded cytoplasm aggregates rapidly in seawater, leading to the formation of protoplasts. However, the genetic basis of the unique cell biology of Bryopsis remains poorly understood. Here, we present a high-quality assembly and annotation of the nuclear genome of Bryopsis sp. (90.7 Mbp, 27 contigs, N50 = 6.7 Mbp, 14,034 protein-coding genes). Comparative genomic analyses indicate that the genes encoding BPL-1/Bryohealin, the aggregation-promoting lectin, are heavily duplicated in Bryopsis, whereas homologous genes are absent in other Ulvophycean algae, suggesting the basis of regeneration capability of Bryopsis. Bryopsis sp. possesses >30 kinesins but only a single myosin, which differs from other green algae that have multiple types of myosin genes. Consistent with this biased motor toolkit, we observed that the bidirectional motility of chloroplasts in the cytoplasm was dependent on microtubules but not actin in Bryopsis sp. Unexpectedly, most genes required for cytokinesis in plants are present in Bryopsis, including those in the SNARE or kinesin superfamily. Nevertheless, a kinesin crucial for cytokinesis initiation in plants (NACK/Kinesin-7II) is hardly expressed in the coenocytic part of the thallus, possibly underlying the lack of cytokinesis in this portion. The present genome sequence lays the foundation for experimental biology in coenocytic macroalgae. Significance statementThe exceptionally coenocytic body and remarkable regeneration ability of Bryopsis have attracted biologists for years. However, molecular biological tools remain underdeveloped, partly due to the lack of genome information. Here, we report high-quality assembly and annotation of the genome, providing a crucial resource for experimental biology and genomics studies of Bryopsis. Furthermore, comparative genomic analysis reveals a unique gene repertoire that possibly underlies the highly regenerative coenocytic body.

plant biology↗

bioRxiv2023

Development of a high throughput system to screen compounds that revert the activated hepatic stellate cells to a quiescent-like state

Chronic liver injury induces fibrosis that often proceeds to cirrhosis and hepatocellular carcinoma, indicating that prevention and/or resolution of fibrosis is a promising therapeutic target. Hepatic stellate cells (HSCs) are the major driver of fibrosis by expressing extracellular matrices (ECM). HSCs, in the normal liver, are quiescent and activated by liver injury to become myofibroblasts that proliferate and produce ECM. It has been shown that activated HSCs (aHSCs) become a "quiescent-like" state by removal of liver insults. Therefore, deactivation agents can be a therapeutic drug for advanced liver fibrosis. Using aHSCs prepared from human induced pluripotent stem cells, we found that aHSCs were reverted to a quiescent-like state by a combination of chemical compounds that either inhibit or activate a signaling pathway, Lanifibranor, SB431542, Dorsomorphin, retinoic acid, palmitic acid and Y27632, in vitro. Based on these results, we established a high throughput system to screen agents that induce deactivation and demonstrate that a single chemical compound can induce deactivation.

cell biology↗

bioRxiv2023

Cell surface architecture of the cultivated DPANN archaeon Nanobdella aerobiophila

The DPANN archaeal clade includes obligately ectosymbiotic species. Their cell surfaces potentially play an important role in the symbiotic interaction between the ectosymbionts and their hosts. However, little is known about the mechanism of the ectosymbiosis. Here, we show cell surface structures of the cultivated DPANN archaeon Nanobdella aerobiophila strain MJ1T and its host Metallosphaera sedula strain MJ1HA, using a variety of electron microscopy techniques, i.e., negative-staining transmission electron microscopy (TEM), quick-freeze deep-etch (QFDE) TEM, and 3D electron tomography. The thickness, unit size, and lattice symmetry of the S-layer of strain MJ1T were different from those of the host archaeon strain MJ1HA. Genomic and transcriptomic analyses highlighted the most highly expressed MJ1T gene for a putative S-layer protein with multiple glycosylation sites and immunoglobulin-like folds, which has no sequence homology to known S-layer proteins. In addition, genes for putative pectin lyase- or lectin-like extracellular proteins, which are potentially involved in symbiotic interaction, were found in the MJ1T genome based on in silico 3D protein structure prediction. Live cell imaging at the optimum growth temperature of 65{degrees}C indicated that cell complexes of strains MJ1T and MJ1HA were motile, but sole MJ1T cells were not. Taken together, we propose a model of the symbiotic interaction and cell cycle of Nanobdella aerobiophila. ImportanceDPANN archaea are widely distributed in a variety of natural and artificial environments, and may play a considerable role in the microbial ecosystem. All of the cultivated DPANN archaea so far need host organisms for their growth, i.e., obligately ectosymbiotic. However, the mechanism of the ectosymbiosis by DPANN archaea is largely unknown. To this end, we performed a comprehensive analysis of the cultivated DPANN archaeon, Nanobdella aerobiophila, using electron microscopy, live cell imaging, transcriptomics, and genomics including 3D protein structure prediction. Based on the results, we propose a reasonable model of the symbiotic interaction and cell cycle of Nanobdella aerobiophila, which will enhance our understanding of the enigmatic physiology and ecological significance of DPANN archaea.

microbiology↗

bioRxiv2023

cycle_finder: de novo analysis of tandem and interspersed repeats based on cycle-finding

Repeat sequences in the genome can be classified into interspersed and tandem repeats, both of which are important for understanding genome evolution and important traits such as disease. They are also noteworthy as regions of high frequency of genome rearrangement in somatic cells and high inter-individual diversity. Existing repeat detection tools have limitations in that they targets only one of the two types and/or require reference sequences. In this study, we developed a novel tool: cycle_finder, which constructs a graph structure (de Bruijn graph) from low-cost short-read data and constructs units of both types of repeats. The tool can detect cycles with branching and corresponding tandem repeats, and can also construct interspersed repeats by exploring non-cycle subgraphs. Furthermore, it can estimate sequences with large copy-number differences by using two samples as input. Benchmarking with simulations and actual data from the human genome showed that this tool had superior recall and precision values compared to existing methods. In a test on the roundworm data, in which large-scale deletions occur in somatic cells, the tool succeeded in detecting deletion sequences reported in previous studies. This tool is expected to enable low-cost analysis of repeat sequences that were previously difficult to construct.

bioinformatics↗