Genome research最新文献_第2页

Genealogy-based trait association with LOCATER boosts power at loci with allelic heterogeneity. 基于家谱的LOCATER性状关联提高了等位基因异质性位点的能力。

IF 5.5 2区生物学

Genome research Pub Date : 2026-05-06 DOI: 10.1101/gr.280372.124

Xinxin Wang, Ryan Christ, Erica Young, Chul Joo Kang, Indraniel Das, Edward A Belter, Markku Laakso, Louis J M Aslett, David Steinsaltz, Nathan O Stitziel, Ira M Hall

{"title":"Genealogy-based trait association with LOCATER boosts power at loci with allelic heterogeneity.","authors":"Xinxin Wang, Ryan Christ, Erica Young, Chul Joo Kang, Indraniel Das, Edward A Belter, Markku Laakso, Louis J M Aslett, David Steinsaltz, Nathan O Stitziel, Ira M Hall","doi":"10.1101/gr.280372.124","DOIUrl":"10.1101/gr.280372.124","url":null,"abstract":"A key methodological challenge for genome-wide association studies is how to leverage haplotype diversity and allelic heterogeneity to improve trait association power, especially in noncoding regions where it is difficult to predict variant impacts and define functional units for variant aggregation. Genealogy-based association methods have the potential to bridge this gap by testing combinations of common and rare haplotypes based purely on their ancestral relationships. In parallel work, we have developed an efficient local ancestry inference engine and a novel statistical method (LOCATER) for combining signals present on different branches of a locus-specific haplotype tree. Here, we develop a genome-wide LOCATER analysis pipeline and apply it to a genome sequencing study of 6795 Finnish individuals with 101 cardiometabolic traits and 18.9 million autosomal variants. We identify 351 significant trait associations at 47 distinct genomic loci and find that LOCATER boosts the single marker test (SMT) association signal at five loci by combining independent signals from distinct alleles. LOCATER successfully recovers known quantitative trait loci not found by SMT, including LIPG, recovers known allelic heterogeneity at the APOE/C1/C4/C2 gene cluster, and suggests one novel association. We find that confounders have a more pronounced effect on genealogy-based methods than SMT, and we propose a new randomization approach and a general method for genomic control to eliminate their effects. This study demonstrates that genealogy-based methods such as LOCATER excel when multiple causal variants are present and suggests that their application to larger and more diverse cohorts will be fruitful.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":"976-991"},"PeriodicalIF":5.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

k-mer cross-species profiling reveals taxon-specific TE expansions accompanied by KZFP co-option and functional impacts in ruminants. k-mer跨物种分析揭示了反刍动物中伴随KZFP共选择和功能影响的分类群特异性TE扩展。

IF 5.5 2区生物学

Genome research Pub Date : 2026-05-06 DOI: 10.1101/gr.281289.125

Pengju Zhao, Jiayi He, Chen Peng, Yuelang Zhang, Chong Wang, Dongyou Yu, Lingzhao Fang, Zhengguang Wang

{"title":"k-mer cross-species profiling reveals taxon-specific TE expansions accompanied by KZFP co-option and functional impacts in ruminants.","authors":"Pengju Zhao, Jiayi He, Chen Peng, Yuelang Zhang, Chong Wang, Dongyou Yu, Lingzhao Fang, Zhengguang Wang","doi":"10.1101/gr.281289.125","DOIUrl":"10.1101/gr.281289.125","url":null,"abstract":"Transposable elements (TEs), which constitute approximately one-third of ruminant genomes, significantly influence genome evolution. However, the substantial sequence diversity across ruminant species complicates cross-species TE comparison and analysis of their interactions with Krüppel-associated box zinc finger proteins (KZFPs). Through a comprehensive analysis of 32 ruminant genomes, we identify taxon-specific expansions of KZFPs (approximately 271 per genome), which reflect established phylogenies. Among TEs, LINE/RTE-BovB dominates genomic content (55.7%), whereas LTR/ERVK subfamilies show significant taxon-specific variation. Our k-mer-based clustering approach effectively reconstructs ruminant phylogeny and reveals temporal patterns of TE expansion. Importantly, we uncover robust coevolutionary signatures between 90 KZFPs and specific TE k-mer clusters, notably involving 32 KZFPs that target Bovidae-specific LTR/ERVK clusters. Furthermore, Bovinae-specific TEs impact gene structure by exonizing 14 genes and generating tissue-enriched cis-regulatory elements (CREs), including 1645 promoter- and enhancer-associated elements. This study establishes a robust computational framework for cross-species TE analysis and provides key insights into the coevolution of KZFPs and TEs, advancing our understanding of TE genomics and function in ruminants.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":"1053-1066"},"PeriodicalIF":5.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-resolution genotype-free mapping of genetic variation with CRI-SPA-Map. 利用crisr - spa - map进行高分辨率无基因型遗传变异定位。

IF 5.5 2区生物学

Genome research Pub Date : 2026-05-06 DOI: 10.1101/gr.281514.125

Sheila Lutz, Megan Lawler, Samuel Amidon, Frank W Albert

{"title":"High-resolution genotype-free mapping of genetic variation with CRI-SPA-Map.","authors":"Sheila Lutz, Megan Lawler, Samuel Amidon, Frank W Albert","doi":"10.1101/gr.281514.125","DOIUrl":"10.1101/gr.281514.125","url":null,"abstract":"Genetic variation within species shapes phenotypes, but identifying the specific genes and variants that cause phenotypic differences is costly and challenging. Here, we introduce CRI-SPA-Map, a genetic mapping strategy combining CRISPR-Cas9 genome engineering, selective ploidy ablation (SPA), and high-throughput phenotyping for precise genetic mapping with or without genotyping in the yeast Saccharomyces cerevisiae In CRI-SPA-Map, a donor strain carrying SPA machinery is mated to a genetically different recipient strain harboring a genome-integrated selectable cassette. In the resulting diploid, CRISPR-Cas9 cuts the cassette for replacement with DNA from the homologous donor chromosome. Donor chromosomes are then removed using SPA to yield haploid recombinant strains. To establish CRI-SPA-Map, we mate a W303 SPA strain to 92 strains from the BY4742 yeast knockout collection that carry gene deletion cassettes on the left arm of Chromosome XIV and create 1451 recombinant isolates. Whole-genome sequencing verifies that deletion cassette replacement introduces short donor DNA tracts of variable length, resulting in a finely recombined mapping population. Using only the known locations of the gene deletions, which mark where donor DNA is introduced, we identify a 6.5 kb region shaping yeast growth. We further dissect this region and identify two causal variants in two genes, MKT1 and SAL1 Engineering these variants alone and in combination reveals gene-by-environment interactions at both genes, as well as epistatic interactions between them that are dependent on the environment. CRI-SPA-Map is a cost-effective, meiosis-free strategy for creating high-resolution recombinant panels of yeast strains for identifying the genetic basis of phenotypic variation.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":"1016-1028"},"PeriodicalIF":5.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A transcriptome-wide systematic search does not detect A-to-I RNA editing in cis-antisense RNA duplexes. 转录组范围的系统搜索没有检测到A-to-I RNA在顺式反义RNA双链中的编辑。

IF 5.5 2区生物学

Genome research Pub Date : 2026-05-06 DOI: 10.1101/gr.280820.125

Zohar Rosenwasser, Roni Cohen-Fultheim, Ofir Shliefer, Erez Y Levanon, Eli Eisenberg

{"title":"A transcriptome-wide systematic search does not detect A-to-I RNA editing in cis-antisense RNA duplexes.","authors":"Zohar Rosenwasser, Roni Cohen-Fultheim, Ofir Shliefer, Erez Y Levanon, Eli Eisenberg","doi":"10.1101/gr.280820.125","DOIUrl":"10.1101/gr.280820.125","url":null,"abstract":"A-to-I RNA editing, catalyzed by the adenosine deaminase acting on RNA (ADAR) enzymes, is a posttranscriptional process that modifies RNA sequences and diversifies the transcriptome. ADARs bind to double-stranded RNA (dsRNA), and their specificity and efficiency are affected by the structural properties of these substructures. In most cases, the dsRNA structure arises from homology between two segments of the same RNA molecule that fold into RNA stem structures. Another possible source of dsRNA is cotranscription of sense and antisense strands of the same genomic region. Binding of these complementary, naturally occurring, antisense transcripts (NATs) results in a perfect RNA duplex, which may be targeted by ADARs. To explore the scope of ADAR editing of NAT-derived dsRNA, we examine editing levels at genome locations where both strands are transcribed. Our findings indicate that editing is rare in regions for which both strands cotranscribe. Moreover, even when RNA editing does occur in NAT regions, it is typically associated with secondary structures on a single strand, suggesting that editing depends on intramolecular structures rather than binding of NATs.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":"916-923"},"PeriodicalIF":5.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-cell template strand sequencing reveals culture-induced chromosomal instability in a gibbon cell line. 单细胞模板链测序揭示了长臂猿细胞系培养诱导的染色体不稳定性。

IF 5.5 2区生物学

Genome research Pub Date : 2026-05-06 DOI: 10.1101/gr.281368.125

Alessia Daponte, Gerardina Chirico, Annalisa Paparella, Annalaura Montanari, Caterina Manzari, Martina Macino, Oliver Dionisi Dyck, Francesco De Leonardis, Flavia Angela Maria Maggiolini, Alberto L'Abbate, Francesco Montinaro, Sandra Louzada, Mario Ventura, Ashley D Sanders, Francesca Antonacci, Claudia Rita Catacchio

{"title":"Single-cell template strand sequencing reveals culture-induced chromosomal instability in a gibbon cell line.","authors":"Alessia Daponte, Gerardina Chirico, Annalisa Paparella, Annalaura Montanari, Caterina Manzari, Martina Macino, Oliver Dionisi Dyck, Francesco De Leonardis, Flavia Angela Maria Maggiolini, Alberto L'Abbate, Francesco Montinaro, Sandra Louzada, Mario Ventura, Ashley D Sanders, Francesca Antonacci, Claudia Rita Catacchio","doi":"10.1101/gr.281368.125","DOIUrl":"https://doi.org/10.1101/gr.281368.125","url":null,"abstract":"Cell lines are invaluable tools for biomedical and evolutionary studies, but their genomic stability over time is often assumed rather than systematically assessed. In this study, we investigate the dynamics of genomic instability and structural rearrangements across multiple batches of a Nomascus siki cell line using a combination of single-cell template strand sequencing (Strand-seq), whole-genome sequencing (WGS), and fluorescence in situ hybridization (FISH). We identify 22 shared inversions in all the Strand-sequenced batches, confirming a common clonal origin. However, we detect additional large-scale rearrangements in all the batches, including trisomy of Chromosome 14 and the formation of isochromosomes of the same chromosome (iso-q and iso-p), leading to the rise of distinct subclonal populations. These rearrangements show evidence of clonal expansion, suggesting a proliferative advantage under in vitro conditions. From an evolutionary perspective, the gibbon genome is known for its exceptional level of chromosomal reshuffling, and this inherent plasticity may have contributed to the cell line's sensitivity to culture-induced structural changes. Despite extensive structural variation, the cell line remains stable at the nucleotide level, with ∼99% of SNPs shared across all batches. Our results illustrate how cell culture can recapitulate aspects of karyotypic evolution and underscore the need for regular genomic surveillance, particularly in long-term cultures. Furthermore, this study demonstrates the power of combining Strand-seq and cytogenetic approaches to detect both balanced and unbalanced rearrangements, especially those present in subclonal populations that would be missed by standard WGS.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"36 5","pages":"938-948"},"PeriodicalIF":5.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Highly efficient and scarless genome editing via essential gene-coupled homology-directed repair. 通过基本基因偶联同源定向修复高效无疤痕基因组编辑。

IF 5.5 2区生物学

Genome research Pub Date : 2026-04-15 DOI: 10.1101/gr.281194.125

Joo Hye Yeo, Hyongbum Henry Kim, Sang Ho Oh, Jinu Lee

{"title":"Highly efficient and scarless genome editing via essential gene-coupled homology-directed repair.","authors":"Joo Hye Yeo, Hyongbum Henry Kim, Sang Ho Oh, Jinu Lee","doi":"10.1101/gr.281194.125","DOIUrl":"https://doi.org/10.1101/gr.281194.125","url":null,"abstract":"Homology-directed repair (HDR) enables precise genome editing; however, its application in mammalian cells is limited by low efficiency due to competition from error-prone repair pathways and intrinsically restricted HDR activity. Existing HDR-enhancement strategies, including small-molecule treatments and marker-based selection, are constrained by cytotoxicity, genomic scarring, and inconsistent performance. Here, we present ESS-HDR (essential gene-supported scarless HDR), a robust, drug- and marker-free platform that selectively enriches HDR-proficient cells. By leveraging essential-gene coediting, ESS-HDR enables precise and scarless genome modification with enhanced efficiency. CRISPR-Cas9 induces double-strand breaks at both the target locus and an essential gene, accompanied by two donor templates: one introducing the desired edit and the other restoring essential-gene function. Only cells that undergo accurate HDR at the essential locus survive, providing endogenous selection without exogenous markers. Single-cell clone analysis confirms that enrichment of HDR-proficient cells enhances editing at the target locus. Using ssODN donors carrying a 1-nt substitution or a 10-nt insertion, ESS-HDR increases HDR efficiencies by 7-16-fold in HEK293 cells and 41-fold in primary epidermal keratinocytes compared to conventional single-site HDR. With plasmid donors targeting TUBA1B, LMNB1, or ACTB1, ESS-HDR improves knock-in efficiencies by 6-34-fold across HEK293, U2OS, and HeLa cells. ESS-HDR also outperforms chemical enhancers including RS-1, SCR7, nocodazole, and AZD7648. Together, these findings establish ESS-HDR as a broadly applicable strategy for efficient, scarless genome editing without external selection markers.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Age-dependent mutational loads in human tRNA genes are tumor-specific and result in chimeric tRNA sequences that could disrupt the genetic code. 人类tRNA基因的年龄依赖性突变负荷是肿瘤特异性的，并导致嵌合tRNA序列，可能破坏遗传密码。

IF 5.5 2区生物学

Genome research Pub Date : 2026-04-15 DOI: 10.1101/gr.281022.125

Marina Murillo, Marina Salvadores, Aina Vaquer Picó, Lina Tsapanou, Adrian Gabriel Torres, Fran Supek, Lluis Ribas de Pouplana

{"title":"Age-dependent mutational loads in human tRNA genes are tumor-specific and result in chimeric tRNA sequences that could disrupt the genetic code.","authors":"Marina Murillo, Marina Salvadores, Aina Vaquer Picó, Lina Tsapanou, Adrian Gabriel Torres, Fran Supek, Lluis Ribas de Pouplana","doi":"10.1101/gr.281022.125","DOIUrl":"https://doi.org/10.1101/gr.281022.125","url":null,"abstract":"Transfer RNA genes (tDNAs) are essential genomic elements that safeguard translational fidelity. Using the T2T version of the human genome we have mapped the position of human tDNAs and analyzed their individual transcriptional activities. Then we have characterized, at single base resolution, the impact of somatic mutations in human tDNAs and its relationship to the transcriptional status of each gene. We confirm that tDNAs are hotspots for somatic mutagenesis, and show that they display mutational loads that are directly proportional to their transcription rates. Highly transcribed tDNAs in tumors or healthy tissues accumulate mutations at rates up to nine-fold higher than highly transcribed protein-coding genes. Mutational loads at tDNAs are tumor-specific, and increase with patient age. Mutations at structurally conserved tRNA positions appear to be under negative selection. Anticodon nucleotides crucial for decoding frequently acquire somatic mutations, readily generating chimeric tRNA species capable of systematically introducing amino acid substitutions across the proteome. Our results reveal a previously unrecognized source of somatic heterogeneity in human cancer and aging tissues that may directly impact upon translation efficiency and fidelity, and cause cell-specific proteostasis degeneration.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Balancing gene ontology annotation specificity in protein function prediction based on the protein sequence large graph. 基于蛋白质序列大图的蛋白质功能预测中基因本体标注特异性的平衡。

IF 5.5 2区生物学

Genome research Pub Date : 2026-04-15 DOI: 10.1101/gr.280816.125

Jiangyi Shao, Shutao Chen, Ziwen Wang, Zixu Chen, Bin Liu

{"title":"Balancing gene ontology annotation specificity in protein function prediction based on the protein sequence large graph.","authors":"Jiangyi Shao, Shutao Chen, Ziwen Wang, Zixu Chen, Bin Liu","doi":"10.1101/gr.280816.125","DOIUrl":"https://doi.org/10.1101/gr.280816.125","url":null,"abstract":"Accurate protein function prediction is fundamental to advancing drug discovery, precision medicine, and understanding complex biological systems. While gene ontology (GO) provides a standardized framework for protein annotation, a critical challenge persists: the imbalance between low-specificity GO terms and high-specificity GO terms. This imbalance creates blind spots in our understanding of protein function landscapes, particularly in clinically relevant pathways. We present ProGO-PSL, a novel large graph architecture designed to resolve this imbalance. ProGO-PSL simultaneously leverages explicit domain identifier from InterPro and implicit evolutionary context from Multiple Sequence Alignments, fusing these complementary data sources within a powerful imbalance learning framework. Our model consistently outperforms state-of-the-art methods by 5-15% across all specificity levels and on both benchmark dataset and independent test set, demonstrating robust generalization. Furthermore, ProGO-PSL generates interpretable representations that clarify relationships between low- and high-specificity GO terms, enabling a more complete functional characterization of the proteome. This work accelerates the identification of therapeutic targets in previously uncharacterized biological pathways.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic characterization of pseudogenes across human tissues. 假基因在人体组织中的表观遗传学特征。

IF 5.5 2区生物学

Genome research Pub Date : 2026-04-15 DOI: 10.1101/gr.280768.125

Yunzhe Jiang, Beatrice Borsari, Mark Gerstein

{"title":"Epigenetic characterization of pseudogenes across human tissues.","authors":"Yunzhe Jiang, Beatrice Borsari, Mark Gerstein","doi":"10.1101/gr.280768.125","DOIUrl":"10.1101/gr.280768.125","url":null,"abstract":"Pseudogenes have historically been regarded as nonfunctional remnants of genome evolution. However, relative to other noncoding genomic elements, their promoter architecture and epigenetic regulation remain incompletely understood. Here, we systematically characterize pseudogene promoters and compare them with those of protein-coding genes and long noncoding RNAs. To do this, we integrate matched transcriptomic and epigenomic data across 26 human tissues from the EN-TEx (ENCODE-GTEx) project. We uniformly annotate promoters with chromatin features (histone modifications, chromatin accessibility, and DNA methylation), sequence motifs, and evolutionary conservation, generating an online catalog. Leveraging this catalog, we show that, across multiple tissues, transcribed, unprocessed pseudogenes exhibit chromatin patterns similar to those of active protein-coding genes. In contrast, transcribed, processed pseudogenes show a different pattern: most lack the canonical hallmarks of transcription (e.g., active histone marks) at their promoters. Instead, their promoters show increased overlap with LINE elements, enrichment for YY1-like binding motifs, and higher Hi-C contact frequency, particularly with distal enhancer-like regulatory regions. Together with their greater conservation (relative to unprocessed pseudogenes), these features suggest that the transcription of processed pseudogenes may require regulatory mechanisms distinct from canonical promoter-associated epigenetic activation.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamics of intronic polyadenylation in the hematopoietic lineage and its regulation by DNA methylation. 造血谱系中的内含子聚腺苷化动力学及其DNA甲基化调控。

IF 5.5 2区生物学

Genome research Pub Date : 2026-04-13 DOI: 10.1101/gr.281044.125

Richa Rashmi, Abhinaya Muruganandham, Pranita Borkar, Sumana Mallick, Taylor Hubbs, Ari Aviles, Daniel Chung, Irtisha Singh

{"title":"Dynamics of intronic polyadenylation in the hematopoietic lineage and its regulation by DNA methylation.","authors":"Richa Rashmi, Abhinaya Muruganandham, Pranita Borkar, Sumana Mallick, Taylor Hubbs, Ari Aviles, Daniel Chung, Irtisha Singh","doi":"10.1101/gr.281044.125","DOIUrl":"https://doi.org/10.1101/gr.281044.125","url":null,"abstract":"Intronic polyadenylation (IPA) is a key mechanism driving transcriptome diversity, yet its detection and functional characterization remain challenging due to complex splicing patterns and complexity of intronic regions. Here, we introduce IPAseek, a dynamic programming-based computational framework that leverages the Pruned Exact Linear Time (PELT) algorithm and Changepoints Over a Range of PenaltieS (CROPS) to enable de novo identification of IPA events from bulk RNA-seq data. IPAseek robustly detects both composite and skipped IPA isoforms. Applying IPAseek to bulk RNA-seq of hematopoietic cell types, reveals lineage and stage-specific IPA signatures, with lymphoid cells exhibiting higher IPA site usage than myeloid cells. Temporal profiling during megakaryocyte differentiation uncovers dynamic, gene-specific IPA regulation linked to functional pathways including peroxisomal metabolism and autophagy which are known to play a crucial role in megakaryocytic differentiation, impacting the development and maturation of megakaryocytes. Further, integrative analysis demonstrates that IPA site usage is associated with lower DNA methylation within introns, supporting a regulatory axis connecting epigenetic state and IPA. This finding aligns with emerging evidence that DNA methylation modulates alternative polyadenylation via CTCF-mediated chromatin looping. Thus, IPAseek provides a platform to characterize IPA across physiological systems and disease contexts using widely available bulk RNA-seq data. These IPA events can be further integrated with other regulatory datasets to elucidate their interplay and functional significance.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147672651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0