Biology subjects

Ou, S.

Publications and source records attributed to Ou, S..

At least 19 recordsLinked to original sources

bioRxiv2026

TIR-Learner v4: Accelerated annotation of terminal inverted repeat transposons

The rapid expansion of high-quality, nearly complete eukaryotic genomes demands computational accelerations of existing bioinformatic infrastructure. TIR-Learner has been widely used for the de novo identification of Terminal Inverted Repeat (TIR) transposons, but suffers from slow runtime and a large memory footprint. Here we present TIR-Learner v4, a complete rewrite of TIR-Learner v3 and key supporting programs, which accelerates runtimes by two orders of magnitude and caps at a low RAM footprint irrespective of genome size. We demonstrate the scalability of TIR-Learner v4 by annotating TIRs in all 579 VGP Phase I genomes in around 4 hours.

bioinformatics↗

bioRxiv2026

EDTA v2: enabling scalable TE annotation in animal genomes

The Extensive de-novo TE Annotator (EDTA) automates transposable element annotation in plant genomes but lacks direct LINE/SINE detection, limiting its applicability to animal genomes. We present EDTA v2, which integrates LINE and SINE detection, completely rewrites TIR-Learner for deployability and scalability, and accelerates structural detectors by up to two orders of magnitude. Tested in 30 animal genomes from the Vertebrate Genomes Project Phase I, EDTA v2 bridges the non-LTR detection gap that has prevented automated TE annotation in animals.

genomics↗

bioRxiv2026

Mapping Tumor-Microenvironment dependencies with TMEformer: A spatial foundation framework enabling in silico perturbation

Despite the fundamental role of spatial context in driving tumor progression, most current computational models for virtual perturbation have largely overlooked its importance. Here, we introduce TMEformer, a tumor microenvironment-aware deep learning framework that leverages high-resolution spatial transcriptomics to jointly model intrinsic tumor cell programs and local microenvironmental signals by explicitly incorporating spatial architecture. Validated across diverse tumor spatial transcriptomic cohorts, TMEformer enables virtual perturbations that capture functional dependencies within local cellular ecosystems. Despite being trained on cancer-specific spatial datasets, TMEformer outperforms baseline models pretrained on large-scale corpora in capturing key tumor transitions, including lineage plasticity and the emergence of therapy resistance. Systematic perturbation analyses prioritize tumor-intrinsic transcription factors and TME-derived ligands that drive disease progression, recovering established regulators and revealing novel candidates. Furthermore, TME- derived embeddings improve the spatial stratification of tumor cells and align more closely with pathological architecture. Together, TMEformer establishes a general framework for modeling tumors as spatially coupled, perturbable ecosystems. An online TMEformer web platform for perturbation prediction, analysis, and visualization is available at http://www.pradcellatlas.com.

bioinformatics↗

bioRxiv2026

The gene-like promoter and transcription of LTR retrotransposons.

Transcriptional regulation is one of the fundamental approaches for young plants to cope with environmental fluctuations and maintain active development. The transposable element (TE) subclass long terminal-repeat retrotransposons (LTR-RTs) can act as additional regulators for genes through enhancer and promoter activity, but their promoters, transcription initiation, and contributions during maize development remain uncharacterized. Here, we developed IsoClassifier to resolve the transcription start site (TSS) and RNA isoforms of LTR-RTs based on long-read transcriptomics, delineating LTR U3 regions as the native promoter and enhancer of LTR-RTs. We reveal conserved motifs associated with core promoter activity in transcribed LTR-RTs that are highly comparable to gene promoters. Further, we found that LTR-RT transcription in maize was dominated by spliced, long non-coding RNA. Finally, a genome-wide coexpression analysis revealed that LTR-RTs are transcribed as hub-like elements in coexpression networks, suggesting important roles in gene regulation. We conclude that LTR-RTs have similar promoter compositions to gene promoters and likely share similar transcription regulation programs.

plant biology↗

bioRxiv2026

TEgenomeSimulator: A Flexible Framework for Simulating Genomes with Configurable Transposable Element Landscapes

Transposable elements (TEs) are major contributors to genome structure and evolution. However, our ability to study them is limited by the difficulty of annotating and curating them, especially in non-model organisms. This challenge is compounded by a lack of ground-truth datasets for benchmarking, which are nearly impossible to generate through manual curation alone. To overcome this critical limitation, we developed TEgenomeSimulator, a flexible framework for generating synthetic genomes with configurable TE landscapes. TEgenomeSimulator supports both randomly generated and biologically derived backbone sequences, enabling the modeling of TE insertions under diverse structural and evolutionary contexts. Benchmarking against existing simulators demonstrated that TEgenomeSimulator reproduces realistic TE composition, sequence divergence, and integrity distributions while offering greater flexibility in modeling chromosome-level structure. Its modular design offers a tuneable continuum between biological fidelity and experimental control, facilitating systematic benchmarking, algorithm development, and evolutionary modeling of TE dynamics in silico, filling a major gap in the field. The source code of TEgenomeSimulator and the scripts for this paper are available at https://github.com/Plant-Food-Research-Open/TEgenomeSimulator.

bioinformatics↗

bioRxiv2025

The complete genome of a songbird

Bird genomes are the smallest among amniotes, but remain challenging to assemble due to their structural complexity. This study presents the first fully phased, diploid, telomere-to-telomere (T2T) reference genome for the zebra finch (Taeniopygia guttata), a model organism for neuroscience and evolutionary genomics. Combining multiple sequencing strategies resulted in closing nearly all gaps, adding [~]90 Mbp of previously missing sequence (7.8%). This includes T2T assemblies for all microchromosomes, including dot chromosomes, and the previously almost entirely missing chr16. The T2T genome is comprehensively annotated for genes, repeats, structural variants, and long-read methylation calls. Complete centromeric structures were assembled and annotated along with kinetochore binding sites. Relative to the previous high-quality reference of the Vertebrate Genomes Project, 2,778 (8.51%) previously unassembled or unannotated genes were identified, of which 9% overlap with segmental duplications. This first complete genome of a songbird, now the new public reference, illuminates avian genome architecture and function.

genomics↗

bioRxiv2025

TESS: A Forward Simulation Framework for Studying the Role of Transposable Elements in Genome Expansion and Contraction

Genome expansion and contraction are reportedly driven by transposable element (TE) activity, but the underlying dynamics remain enigmatic due to a lack of historical records tracing these changes. Here, we present PrinTE for versatile, forward-time simulation of whole-genome sequences with highly customizable transposon dynamics. Through simulations, we confirm that the distribution of TE sequence divergence reflects their historical insertion and deletion dynamics, which can be used to infer TE dynamic parameters through PrinTE simulations. We analyzed the pangenome of Pucciniomycotina, a subdivision of fungi containing myrtle rust (Austropuccinia psidii), which drastically expanded its genome size to 1018 Mb. Our analyses reveal that the best strategy for controlling genome size is to avoid the invasion of LTR retrotransposons (LTR-RTs). While illegitimate recombination (IR) is considered the most effective counteraction of LTR-RT invasions leaving only solo LTR remnants, we observed a strong positive correlation between solo:intact LTR ratio (strength of LTR-RT removal) and genome size (r = 0.65), and a near-linear correlation between solo LTR count and genome size (r = 0.98). This result suggests that IR alone may not effectively prevent genome obesity. Through simulation of Pucciniomycotina genomes, we proposed that A. psidii might experience a prolonged period of genome expansion followed by a short, potent, and likely ongoing period of contraction. PrinTE is freely available at https://github.com/cwb14/PrinTE.git.

bioinformatics↗

bioRxiv2024

Solanum pan-genomics and pan-genetics reveal paralogs as contingencies in crop engineering

Pan-genomics and genome editing technologies are revolutionizing the breeding of globally cultivated crops. A transformative opportunity lies in the reciprocal exchange of genotype-to-phenotype knowledge of agricultural traits between these major crops and hundreds of locally cultivated indigenous crops, thereby enhancing the diversity and resilience of our food system. However, species-specific genetic variants and their interactions with desired natural or engineered mutations pose barriers to achieving predictable phenotypic effects, even between closely related crops or genotypes. Here, by establishing a pan-genome of the crop-rich genus Solanum and integrating functional genomics and genetics, we show that gene duplication and subsequent paralog diversification are a major obstacle to genotype-phenotype predictability. Despite broad conservation of gene macrosynteny among chromosome-scale references for 22 species, including 13 indigenous crops, hundreds of global and lineage-specific gene duplications exhibited dynamic evolutionary trajectories in paralog sequence, expression, and function, including among members of key domestication gene families. Extending our pan-genome with 10 cultivars of African eggplant and leveraging quantitative genetics and genome editing, we uncovered an intricate history of paralog emergence and evolution within this indigenous crop. The loss of an ancient redundant paralog of the classical regulator of stem cell proliferation and fruit organ number, CLAVATA3 (CLV3), was compensated by a lineage-specific tandem duplication. Subsequent pseudogenization of the derived copy followed by a cultivar-specific structural variant resulted in a single fused functional copy of CLV3 that modifies locule number alongside a newly identified gene controlling the same trait. Our findings demonstrate that paralog diversifications over short evolutionary periods are critical yet underexplored contingencies in trait evolvability and independent crop domestication histories. Unraveling these contingencies is crucial for translating genotype-to-phenotype relationships across related species.

genetics↗

bioRxiv2024

Center-surround inhibition by expectation: a neuro-computational account

Expectation is beneficial for adaptive behavior through quickly deducing plausible interpretations of information. The profile and underlying neural computations of this process, however, remain unclear. When participants expected a grating with a specific orientation, we found a center-surround inhibition profile in orientation space, which was independent from attentional modulations by task-relevance. Using computational modeling, we showed that this center-surround inhibition could be reproduced by either a sharpening of tuning curves of expected orientation or a shift of tuning curves of unexpected orientations. Intriguingly, these two computations were further supported by orientation-adjustment and orientation-discrimination experiments. Finally, the ablation studies in convolutional neural networks revealed that predictive coding feedback played a critical role in the center-surround inhibition in expectation. Altogether, our study reveals for the first time that expectation results in both enhancement and suppression, optimizing plausible interpretations during perception by enhancing expected and attenuating similar but irrelevant and potentially interfering representations.

neuroscience↗

bioRxiv2024

Deciphering octoploid strawberry evolution with serial LTR similarity matrices for subgenome partition

Polyploidization has been recognized as a major force in plant evolution. With the continuous progress in sequencing technologies and genome assembly algorithms, high-quality chromosome-level assemblies of polyploid genomes have become increasingly attainable. However, accurately delineating these assemblies into subgenomes remains a challenging task, especially in case where known diploid ancestors are absent. In this study, we introduce a novel approach that leverages long terminal repeat retrotransposons (LTR-RTs) coupled with the Serial Similarity Matrix (SSM) method to assign genome assemblies to subgenomes, particularly beneficial for those without known diploid progenitor genomes. The SSM method helps identify subgenome-specific LTRs and facilitates the inference of the timing of allopolyploidization events. We validated the efficacy of the SSM approach using well-studied allopolyploidy genomes, Eragrostis tef and Gossypium hirsutum, alongside an artificially created allotetraploid genome by merging two closely related diploid species, Glycine max and G. soja. Our results demonstrated the robustness of the method and its effectiveness in assigning chromosomes to subgenomes. We then applied the SSM method to the octoploid strawberry genome. Our analysis revealed three allopolyploidization events in the evolutionary trajectory of the octoploid strawberry genome, shedding light on the evolutionary process of the origin of the octoploid strawberry genome and enhancing our understanding of allopolyploidization in this complex species.

bioinformatics↗

bioRxiv2024

TEtrimmer: a novel tool to automate the manual curation of transposable elements

Transposable elements (TEs) are repetitive DNA sequences capable of moving within genomes. Accurate annotation and classification of TEs is crucial but challenging due to their sequence diversity and often fragmented occurrence. We present TEtrimmer, a novel tool to automate manual TE curation. TEtrimmer integrates multiple sequence alignment (MSA) clustering, MSA sequence extension, MSA cleaning, TE boundary definition, and TE classification, and provides report plots and a graphical user interface (GUI) application to inspect and improve results. Benchmarked on the genomes of six organisms from various kingdoms of life, TEtrimmer consistently improved the identification of intact TEs compared to established tools.

bioinformatics↗

bioRxiv2024

Gapless assembly of complete human and plant chromosomes using only nanopore sequencing

The combination of ultra-long Oxford Nanopore (ONT) sequencing reads with long, accurate PacBio HiFi reads has enabled the completion of a human genome and spurred similar efforts to complete the genomes of many other species. However, this approach for complete, "telomere-to-telomere" genome assembly relies on multiple sequencing platforms, limiting its accessibility. ONT "Duplex" sequencing reads, where both strands of the DNA are read to improve quality, promise high per-base accuracy. To evaluate this new data type, we generated ONT Duplex data for three widely-studied genomes: human HG002, Solanum lycopersicum Heinz 1706 (tomato), and Zea mays B73 (maize). For the diploid, heterozygous HG002 genome, we also used "Pore-C chromatin contact mapping to completely phase the haplotypes. We found the accuracy of Duplex data to be similar to HiFi sequencing, but with read lengths tens of kilobases longer, and the Pore-C data to be compatible with existing diploid assembly algorithms. This combination of read length and accuracy enables the construction of a high-quality initial assembly, which can then be further resolved using the ultra-long reads, and finally phased into chromosome-scale haplotypes with Pore-C. The resulting assemblies have a base accuracy exceeding 99.999% (Q50) and near-perfect continuity, with most chromosomes assembled as single contigs. We conclude that ONT sequencing is a viable alternative to HiFi sequencing for de novo genome assembly, and has the potential to provide a single-instrument solution for the reconstruction of complete genomes.

bioinformatics↗

bioRxiv2024

Accelerating de novo SINE annotation in plant and animal genomes

Genome annotation is an important but challenging task. Accurate identification of short interspersed nuclear elements (SINEs) is particularly difficult due to their lack of highly conserved sequences. AnnoSINE is state-of-the-art software for annotating SINEs in plant genomes, but its homology-based module is not available for animals and it is computationally inefficient for large genomes. Therefore, we propose AnnoSINE_v2, which extends accurate SINE annotation for animal genomes with greatly optimized computational efficiency. Our results show that AnnoSINE_v2s annotation of SINEs has over 20% higher F1-score compared to the existing tools on animal genomes and enables the processing of complicated genomes, like human and zebrafish, which were beyond the capabilities of AnnoSINE_v1. AnnoSINE_v2 is freely available on Conda and GitHub: https://github.com/liaoherui/AnnoSINE_v2.

bioinformatics↗

bioRxiv2023

Genome of the North American wild apple species Malus angustifolia

Apple (Malus x domestica Borkh.) production faces many challenges stemming from abiotic and biotic stresses. Abiotic stressors, such as extreme temperatures, droughts, and spring frosts, can lead to diminished yields and tree loss, while biotic stresses like fire blight and pest infestations further reduce tree health and fruit quality. To lessen the threat of these challenges, plant breeders aim to introduce resistance and resilience genes into cultivated varieties. However, high-relatedness among cultivated varieties and breeding lines, coupled with the long juvenility and generation times in apples, hinder the breeding process. The introduction of resistance traits from wild relatives is also constrained by these factors, as well as the lack of genomic resources that could assist in accelerating the introgression process. Herein, we report the assembly and annotation of Malus angustifolia, the Southern Crabapple, one of Eastern North Americas native species. Using a combination of Pacific Biosciences High Fidelity reads, Next-generation short read sequencing, as well as chromatin conformation capture sequencing, we achieve an extremely contiguous haplotype-resolved assembly. We perform comparative haplotypic analyses to identify SNPs and large structural variants, shedding light on the genomic landscape of M. angustifolia. Finally, we explore the phylogenetic and syntenic relationships between Eurasian Malus progenitors and the recently sequenced North American species, contributing valuable insights to the broader understanding of apple evolution and potential breeding strategies.

genomics↗

bioRxiv2023

The genome of the Wollemi pine, a critically endangered living fossil unchanged since the Cretaceous, reveals extensive ancient transposon activity.

We present the genome of the living fossil, Wollemia nobilis, a southern hemisphere conifer morphologically unchanged since the Cretaceous. Presumed extinct until rediscovery in 1994, the Wollemi pine is critically endangered with less than 60 wild adults threatened by intensifying bushfires in the Blue Mountains of Australia. The 12 Gb genome is among the most contiguous large plant genomes assembled, with extremely low heterozygosity and unusual abundance of DNA transposons. Reduced representation and genome re-sequencing of individuals confirms a relictual population since the last major glacial/drying period in Australia, 120 ky BP. Small RNA and methylome sequencing reveal conservation of ancient silencing mechanisms despite the presence of thousands of active and abundant transposons, including some transferred horizontally to conifers from arthropods in the Jurassic. A retrotransposon burst 8-6 my BP coincided with population decline, possibly as an adaptation enhancing epigenetic diversity. Wollemia, like other conifers, is susceptible to Phytophthora, and a suite of defense genes, similar to those in loblolly pine, are targeted for silencing by sRNAs in leaves. The genome provides insight into the earliest seed plants, while enabling conservation efforts.

genomics↗

bioRxiv2023

A haplotype resolved chromosome-scale assembly of North American wild apple Malus fusca and comparative genomics of the fire blight Mfu10 locus.

The Pacific crabapple (Malus fusca) is a wild relative of the commercial apple (Malus x domestica). With a range extending from Alaska to Northern California, M. fusca is extremely hardy and disease resistant. The species represents an untapped genetic resource for development of new apple cultivars with enhanced stress resistance. However, gene discovery and utilization of M. fusca has been hampered by the lack of genomic resources. Here, we present a high-quality, haplotype-resolved, chromosome-scale genome assembly and annotation for M. fusca. The genome was assembled using high-fidelity long-reads and scaffolded using genetic maps and high-throughput chromatin conformation capture sequencing, resulting in one of the most contiguous apple genomes to date. We annotated the genome using public transcriptomic data from the same species taken from diverse plant structures and developmental stages. Using this assembly, we explored haplotypic structural variation within the genome of M. fusca, identifying thousands of large variants. We further showed high sequence co-linearity with other domesticated and wild Malus species. Finally, we resolve a known quantitative trait locus associated with resistance to fire blight (Erwinia amylovora). Insights gained from the assembly of a reference-quality genome of this hardy wild apple relative will be invaluable as a tool to facilitate DNA-informed introgression breeding.

genomics↗

bioRxiv2022

Differences in activity and stability drive transposable element variation in tropical and temperate maize.

Much of the profound interspecific variation in genome content has been attributed to transposable elements (TEs). To explore the extent of TE variation within species, we developed an optimized open-source algorithm, panEDTA, to de novo annotate TEs in a pan-genome context. We then generated a unified TE annotation for a maize pan-genome derived from 26 reference-quality genomes, which revealed an excess of 35.1 Mb of TE sequences per genome in tropical maize relative to temperate maize. A small number (n = 216) of TE families, mainly LTR retrotransposons, drive these differences. Evidence from the methylome, transcriptome, LTR age distribution, and LTR insertional polymorphisms revealed that 64.7% of the variability was contributed by LTR families that were young, less methylated, and more expressed in tropical maize, while 18.5% was driven by LTR families with removal or loss in temperate maize. This study demonstrates the use of a comprehensive pan-TE annotation to reveal the driving role of TEs in within-species genomic variation via their ongoing amplification and purging.

genomics↗

bioRxiv2022

Modbamtools: Analysis of single-molecule epigenetic data for long-range profiling, heterogeneity, and clustering

The advent of long-read sequencing methods provides new opportunities for profiling the epigenome - especially as the methylation signature comes for "free" when native DNA is sequenced on either Oxford Nanopore or Pacific Biosciences instruments. However, we lack tools to visualize and analyze data generated from these new sources. Recent efforts from the GA4GH consortium have standardized methods to encode modification location and probabilities in the BAM format. Leveraging this standard format, we developed a technology-agnostic tool, modbamtools to visualize, manipulate and compare base modification/methylation data in a fast and robust way. modbamtools can produce high quality, interactive, and publication-ready visualizations as well as provide modules for downstream analysis of base modifications. Modbamtools comprehensive manual and tutorial can be found at https://rrazaghi.github.io/modbamtools/.

bioinformatics↗