Jiang Hu

Summary: Long-read sequencing (LRS) has become essential for genome assembly, structural variations (SVs) detection, haplotype phasing and transcript isoform characterization. However, these applications often require manual inspection of read alignment for validation. Existing visualization tools are either interactive genome browsers that are difficult to scale to large datasets or batch-oriented tools that are not optimized for the unique alignment patterns of long-read data. We developed Bamsnap-LRS, an automated command-line tool for high-throughput LRS alignment visualization. It supports long-read-specific features, phased SNP inspection, and publication-ready batch figure generation within a unified framework for genomic, transcriptomic, and haplotype-aware analyses. Availability and Implementation: All codes and examples are freely available at https://github.com/comery/Bamsnap-LRS.

Long-read mapping performance is critical for downstream genomic analyses but remains sensitive to parameter selection. We present CycSim, a context-aware long-read simulator that learns sequence-context-dependent error profiles from empirical data and generates realistic simulated reads. CycSim more faithfully recapitulated real long-read characteristics than existing simulators, providing a high-fidelity simulation framework with known ground truth. Using this framework, we identified a Cyclone-specific parameter set that achieved 2.78-fold faster mapping than an ONT-oriented baseline while maintaining comparable variant-calling performance. For SV-oriented optimization, CycSim-guided refinement improved mapping efficiency by 8.14–34.16% across ONT, HiFi, and Cyclone HG002 datasets; increased SV F1 scores by 0.57–1.75 percentage points; and showed consistent improvements across independent benchmark datasets and different SV callers. Together, these results demonstrate the utility of CycSim for platform- and analysis-goal-specific algorithm development, benchmarking, and parameter optimization.

Hibernation is an adaptive survival strategy used by animals to cope with extreme environmental conditions. Although this physiological process involves complex metabolic changes, its underlying biological mechanisms remain largely unknown. Through comparative genomic analysis of six hibernating species across five orders, we identified an ancient amino acid substitution in POMT2 (R708Q), exhibiting signals of both convergent and positive selection in hibernating mammals. Phylogenetic analysis using HeIST indicated hemiplasy as a possible explanation, though given mammalian divergence times and the broader evidence for convergence, this is best considered an alternative rather than the primary interpretation. Functional studies using transgenic mice demonstrated the contribution of this mutation to hypoxia adaptation. Notably, despite the absence of this mutation in Rodentia hibernators, we included Graphiurus kelleni as a positive control in physiological studies of transgenic mice carrying POMT2(R708Q), given its remarkable hypoxia adaptation during hibernation. Our findings not only provide novel insights into the genetic basis of hypoxic adaptation in hibernating mammals but also suggest incomplete lineage sorting (hemiplasy) as a plausible evolutionary mechanism for this important adaptive trait.

The performance of long-read mapping is critical yet highly sensitive to parameter choices. We present CycSim, a context-aware simulator that models sequence-context-dependent errors from empirical sequencing data, coupled with a Bayesian optimization framework for systematic parameter tuning. CycSim more accurately reproduces real error profiles than existing simulators, enabling reliable simulation-based optimization. The framework identified parameter configurations that achieved 2.78-fold faster mapping for data from the newly developed Cyclone platform, and consistently improved both mapping efficiency (8.14-32.65% faster) and structural variant calling accuracy (0.75-1.70% higher F1) across ONT, HiFi, and Cyclone datasets, providing a robust and generalizable foundation for analysis-goal-driven parameter refinement.

The high-fidelity (HiFi) long-read sequencing technology developed by PacBio has greatly improved the base-level accuracy of genome assemblies. However, these assemblies still contain base-level errors, particularly within the error-prone regions of HiFi long reads. Existing genome polishing tools usually introduce overcorrections and haplotype switch errors when correcting errors in genomes assembled from HiFi long reads. Here, we describe an upgraded genome polishing tool — NextPolish2, which can fix base errors remaining in those “highly accurate” genomes assembled from HiFi long reads without introducing excessive overcorrections and haplotype switch errors. We believe that NextPolish2 has a great significance to further improve the accuracy of telomere-to-telomere (T2T) genomes. NextPolish2 is freely available at https://github.com/Nextomics/NextPolish2.

The purpose of this study was to determine the mechanism of Astragalus activity on the immune function, rumen microbiota structure and rumen fermentation of early-weaned lambs. Thirty healthy early-weaned lambs with similar body weights (17.42 ± 2.02 kg) were selected for the feeding experiment. The control group (KB) was fed a basal diet, and the Astragalus group (HQ) was fed 0.3% Astragalus additive on the basis of a basic diet. The formal trial period was 60 days. The results showed that the concentrations of blood immunoglobulin A (IgA) and immunoglobulin M (IgM) in the HQ group were significantly higher than those in the KB group (P<0.05). Compared with the KB group, the concentrations of acetic acid, butyric acid and total volatile fatty acids (VFAs) in the HQ group were higher (PMCT1, MCT4, NHE2 and ZO1 in the Astragalus group were significantly higher than those in the KB group (PPPrevotella (PSucciniclasticum (PP<0.05). As a feed additive, Astragalus can improve the immunity of early-weaned lambs, the structure of the rumen microbiota of lambs, and the fermentation capacity of the rumen.

Since its initial release in 2001, the human reference genome has undergone continuous improvement in quality, and the recently released telomere-to-telomere (T2T) version — T2T-CHM13 — reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified, nearly homozygous genome of a hydatidiform mole cell line. Here, to provide an authentic complete diploid human genome reference for the Han Chinese, the largest population in the world, we assembled the genome of a male Han Chinese individual, T2T-YAO, which includes T2T assemblies of all the 22 + X + M and 22 + Y chromosomes in both haploids. The quality of T2T-YAO is much better than those of all currently available diploid assemblies, and its haploid version, T2T-YAO-hp, generated by selecting the better assembly for each autosome, reaches the top quality of fewer than one error per 29.5 Mb, even higher than that of T2T-CHM13. Derived from an individual living in the aboriginal region of the Han population, T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors. Each haplotype of T2T-YAO possesses ∼ 330-Mb exclusive sequences, ∼ 3100 unique genes, and tens of thousands of nucleotide and structural variations as compared with CHM13, highlighting the necessity of a population-stratified reference genome. The construction of T2T-YAO, an accurate and authentic representative of the Chinese population, would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes, especially within the context of the unique variations of the Chinese population.

Comparative analysis of primate genomes within a phylogenetic context is essential for understanding the evolution of human genetic architecture and primate diversity. We present such a study of 50 primate species spanning 38 genera and 14 families, including 27 genomes first reported here, with many from previously less well represented groups, the New World monkeys and the Strepsirrhini. Our analyses reveal heterogeneous rates of genomic rearrangement and gene evolution across primate lineages. Thousands of genes under positive selection in different lineages play roles in the nervous, skeletal, and digestive systems and may have contributed to primate innovations and adaptations. Our study reveals that many key genomic innovations occurred in the Simiiformes ancestral node and may have had an impact on the adaptive radiation of the Simiiformes and human evolution.

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil containing a high proportion of eleostearic acid (∼80%). Here we report a high-quality, chromosome-scale tung tree genome sequence of 1.12 Gb with 28,422 predicted genes and over 73% repeat sequences. Tung tree genome was assembled by combining Illumina short reads, PacBio single-molecule real-time long reads and Hi-C sequencing data. Insertion time analysis revealed that the repeat-driven tung tree genome expansion might be due to long standing long terminal repeat (LTR) retrotransposon bursts and lack of efficient DNA deletion mechanisms. An electronic fluorescent pictographic (eFP) browser was generated based on genomic and RNA-seq data from 17 various tissues and developmental stages. We identified 88 nucleotide-binding site (NBS)-encoding resistance genes, of which 17 genes may help the tung tree resist theFusariumwilt shortly after infection. A total of 651 oil-related genes were identified and 88 of them were predicted to be directly involved in tung oil biosynthesis. The fewer phosphoenolpyruvate carboxykinase (PEPC) genes, and synergistic effects between transcription factors and oil biosynthesis-related genes may contribute to high oil content in tung seeds. The tung tree genome should provide valuable resources for molecular breeding and genetic improvement.

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Biosciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree genome is 1.12 Gb, with 28,422 predicted genes and over 73% repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites; 17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effects between transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.