Genome Biology最新文献

Background: The floral transition in maize represents a pivotal developmental switch that determines flowering time, environmental adaptation, and yield-related traits. However, the molecular mechanisms governing shoot apical meristem reprogramming and cell identity changes during this process remain poorly understood.

Results: By integrating time-course bulk RNA-seq, single-cell transcriptomics, chromatin accessibility, and transcription factor binding profiles, we construct a spatiotemporal molecular framework of the maize shoot apical meristem floral transition. Our analyses reveal global transcriptional reprogramming accompanied by pronounced cell type-specific regulation dynamics. At a global level, our transcriptional-level inference suggests that pathways associated with chromatin remodeling, environmental response, and reproductive development are sequentially activated. We further identify a ZmMADS69-ZmRap2.7-ZMM4 regulatory module that fine-tunes the floral transition within the shoot apical meristem. At single-cell resolution, we find that the floral transition is not driven by a uniform transcriptional switch, but instead emerges from the coordinated action of spatially distinct shoot apical meristem domains. Through differential expression, trajectory, and co-expression module analyses, we further identify previously unrecognized roles for the inflorescence regulators UNBRANCHED2 and UNBRANCHED3 in promoting the floral transition, suggesting that they coordinate floral induction with subsequent inflorescence development.

Conclusions: Our study establishes a comprehensive spatiotemporal regulatory framework for the maize floral transition, providing mechanistic insights into shoot apical meristem reprogramming and offering a foundation for identifying new regulators to improve maize adaptation and yield.

Long-read transcriptome sequencing (long-RNA-seq) revolutionizes transcriptome research by enabling full-length transcript analysis for comprehensive exploration of isoform diversity. We developed IFDlong, a probabilistic framework and software suite for detecting isoform and fusion transcripts from bulk or single-cell long-RNA-seq data. IFDlong annotates each long read, identifies novel isoforms, quantifies expression via an expectation-maximization algorithm, and profiles fusion transcripts. In large-scale simulation and real data analyses, IFDlong outperforms existing tools and demonstrated high accuracy and robustness across multiple in-house and public datasets, including healthy tissues, cell lines, and different diseases.

Background: The integration of multimodal single-cell data enables comprehensive organ reference atlases, yet its impact remains largely unexplored, particularly in complex tissues. Using the kidney as an emblematic example of a complex organ, we perform a systematic evaluation of multimodal single-cell integration strategies, with heart tissue used for additional methodological validation.

Results: We generate a benchmarking dataset for the renal cortex by integrating 3' and 5' scRNA-seq with joint snRNA-seq and snATAC-seq, profiling 119,744 high-quality nuclei/cells from 19 donors. To align cell identities and enable consistent comparisons, we develop the interpretable machine learning tool scOMM (single-cell Omics Multimodal Mapping) and systematically assess integration strategies. "Horizontal" integration of scRNA and snRNA-seq improves cell-type identification, while "vertical" integration of snRNA-seq and snATAC-seq has an additive effect, enhancing resolution in homogeneous populations and difficult-to-identify states. Global integration is especially effective in identifying adaptive states and rare cell types, including WFDC2-expressing Thick Ascending Limb and Norn cells, previously undetected in kidney atlases.

Conclusions: Our work establishes a robust framework for multimodal reference atlas generation, advancing single-cell analysis and extending its applicability to diverse tissues.

Background: Sex chromosome turnovers evolve via translocation or duplication of established sex-determining genes, or their replacement by newly evolved ones. Few cases of replacements by new factors have been documented in dioecious plants, but are suspected in Salix, in which both XY and ZW systems occur, with sex-linked regions (SLRs) of different species on various chromosomes. The male-determining genes in XY species' SLRs are partial duplicates of autosomal ARR17-like genes and regulate the expression of downstream genes involved in stamen development by producing small RNAs that suppress the expression of intact copies.

Results: Here we describe phased chromosomal assemblies of three Salix species with a ZW system derived from an XY system, including four lineages of the Salix polyclona complex (six assemblies in total). Their SLRs are within the same repeat-rich pericentromeric region of chromosome 15 as in the willows with XY system. Although these Z- and W- SLRs carry intact and/or partial ARR17 duplicates, few RNA products are detectable in our sampled tissues. However, the W-SLRs include partial duplicates of PISTILLATA (PI), a stamen development gene. These are arranged in inverted repeats and express small interfering RNAs targeting the autosomal intact Salix PI gene, suggesting that they reduce its expression, and therefore act as maleness-suppressing factors.

Conclusions: The turnover events involving intact ARR17 and partial PI duplications in the 15ZW clade I species involve pericentromeric regions that recombine rarely, making changes possible in these Salix species that would be unlikely in other genome regions.

Background: Streptococcus mutans is a member of the human oral microbiota and is considered one of the most important cariogenic organisms. Previous studies have suggested an expansion of S. mutans populations about 10,000 years ago with the onset of agriculture, yet direct molecular evidence of its presence from ancient DNA remains sparse.

Results: Here, we present population genomic analyses of 25 ancient S. mutans genomes (average read depth 0.1X - 387X) recovered from archaeological remains across Eurasia spanning ~ 8,000 years of human evolution. Recombination-corrected phylogenomic analyses using Gubbins show a star-like phylogeny indicative of an early radiation, with the ancient genomes falling within the genomic diversity of modern isolates but restricted to one of the major clades of the phylogeny (D). Analyses of genes encoding present day virulence factors reveals that the presence of the mutanobactin operon involved in oxygen tolerance is restricted to specific subclades (A & B) and absent among the ancient samples. Using the MEGAHIT assembler followed by binning of contigs with CONCOCT, we recover metagenome-assembled genomes (MAG) of 7 high-coverage ancient S. mutans strains, including a 7,500-year-old sample from an early European Neolithic farmer. Pangenome analysis with modern isolates using the anvi'o's suite revealed the presence of specific functional genes in the ancient isolates, which were lost through time.

Conclusions: Our study demonstrates that Streptococcus mutans DNA is well preserved in tooth samples from archaeological remains and show that it formed part of the human oral microbiota already before the onset of agriculture, consistent with a radiation and population expansion well before 8,000 years ago.

The circulating blood proteome comprises soluble and cellular components that reflect physiological and pathological states across tissues. Advances in mass spectrometry and affinity-based proteomics have improved sensitivity and throughput, enabling the generation of public blood proteomics resources. However, comprehensive assessments of these datasets remain limited. This work reviews the cellular and molecular complexity of publicly available blood proteomics data, recent methodological developments, and the complementarity of diverse data sources across the abundance range, while outlining remaining challenges for translating blood proteomics into personalized medicine.

Background: Studying a new species using high-throughput sequencing requires a high-quality reference genome. However, assembling chromosome length sequences remains challenging. Recent advances in chromatin conformation capture (Hi-C) have provided a new approach to scaffolding genome assemblies, and the last ten years have seen a proliferation of such methods. However, to our knowledge no comprehensive benchmarking of Hi-C scaffolders has been conducted to date.

Results: Through a literature review we identify the most popular Hi-C scaffolders - Lachesis, HiRise, 3d-dna, SALSA, and AllHiC. We test their ability to scaffold four well studied genomes - S. cerevisiae, L. tarentolae, A. thaliana, and H. sapiens. Scaffolders are tasked with both scaffolding fragmented versions of the reference genome as well as de novo assemblies derived from long read datasets. We find that all scaffolders can exceed 80% accuracy under ideal circumstances but that their performance quickly deteriorates under more challenging conditions. Surprisingly, many scaffolders also show poor performance on the best assemblies, where contigs are near chromosome length. Overall, we find that HiRise and Lachesis offer the best performance on average across all conditions.

Conclusions: We compare the performance of five Hi-C scaffolders using multiple reference species under both ideal and real-life conditions, thereby illuminating their strengths and weaknesses.

Background: Tandemly repeated satellite DNAs (satDNAs) are among the most copious sequences of eukaryotic genomes. They often reside in centromeric regions, but their diversity among different organisms obscures the properties that centromere-competent satDNAs should possess.

Results: Here, we explore the satellitome of the satDNA-rich flour beetle Tribolium madens. By combining short-read Illumina and long-read PacBio HiFi sequencing, we identify 124 satDNAs comprising 41.4% of the genome. We find that 38% of the genome sequence originates from a ~ 110 bp element that gives rise to two distinct satDNAs, the major and minor satellites, which occupy multi-megabase regions likely encompassing (peri)centromeres of all chromosomes. Fine-scale analysis of long-range organization reveals that intermingled arrays of the major and minor satDNAs are arranged in macro-dyad symmetries with the potential to form hairpin or cruciform structures spanning tens of kilobases. The inversion sites within macro-dyad symmetries and the transition zones between the major and minor satDNA arrays are highly conserved, indicating structural significance. The organization of the Tribolium madens putative (peri)centromeric satDNAs is comparable to that of the closely related Tribolium freemani and Tribolium castaneum, whose completely different dominant satDNAs also incline toward macro-dyad symmetries.

Conclusions: We propose that satDNA-related macro-dyad symmetries may affect the organization of (peri)centromeric chromatin, potentially also influencing centromere specification. The analogous pattern in congeners suggests that such symmetries are an intrinsic feature of Tribolium (peri)centromeric regions, implying that repeat organization and potential non-canonical DNA structures could be functionally more significant than the primary sequence of satDNA repeats.

Background: Centromere identity in eukaryotes is defined epigenetically by CENH3 (CENPA), a specialized histone H3 variant essential for kinetochore establishment and faithful chromosome segregation. However, the regulatory mechanisms governing CENH3 loading during meiosis and how they differ from mitotic patterns remain insufficiently elucidated.

Results: Here we characterize the dynamics of CENH3 deposition across meiosis and compare them with mitotic loading in rice. Quantitative fluorescence imaging reveals a pronounced increase of CENH3 signal during meiotic prophase I, coinciding with increased accumulation of multiple kinetochore components. Super-resolution stimulated emission depletion microscopy further confirms a distinct peak of CENH3 loading at zygotene. Through low-input ChIP-seq integrated with multi-omics profiling of purified meiocytes, we find that this meiosis-specific enrichment reflects both expanded and intensified CENH3 deposition, predominantly at Ty3-Gypsy retrotransposons. This remodeling is accompanied by reduced transcription of mRNAs and small RNAs, along with a reduction in CHG methylation and H3K9me2 heterochromatin marks.

Conclusion: Our findings uncover a previously unrecognized, meiotic-specific pattern of CENH3 loading in rice and highlight a coordinated regulatory network linking centromeric chromatin reorganization, transcriptional repression, and epigenetic modification during early meiotic progression.

A key step in sequence similarity search is to identify shared seeds between a query and a reference sequence. A well-known tradeoff is that longer seeds offer fast searches but reduce sensitivity in variable regions. We introduce multi-context seeds (MCS), which allow the storage of seeds with different lengths in the same index structure, thus retaining the advantages of both short and long seeds. We demonstrate the applicability of MCS by implementing them in strobealign. Strobealign with MCS substantially improves accuracy compared to the previous version with little cost in runtime and no memory overhead.