Mammalian Genome最新文献_第3页

Neuroinflammation in glaucoma: a myriad of cellular pathways and players. 青光眼的神经炎症：无数的细胞通路和参与者。

IF 2.6 4区生物学

Mammalian Genome Pub Date : 2026-06-27 DOI: 10.1007/s00335-026-10253-0

Michael MacLean, Sean D Lydon, Cátia Gomes, Elizabeth M Pizzi, Cory A Diemler, Sarah E R Yablonski, Gareth R Howell, Jason S Meyer, Richard T Libby

{"title":"Neuroinflammation in glaucoma: a myriad of cellular pathways and players.","authors":"Michael MacLean, Sean D Lydon, Cátia Gomes, Elizabeth M Pizzi, Cory A Diemler, Sarah E R Yablonski, Gareth R Howell, Jason S Meyer, Richard T Libby","doi":"10.1007/s00335-026-10253-0","DOIUrl":"10.1007/s00335-026-10253-0","url":null,"abstract":"Glaucoma is a complex neurodegenerative disease with multiple subtypes, yet all are characterized by the progressive dysfunction and loss of retinal ganglion cells (RGCs), which ultimately results in vision impairment and blindness. Elevated intraocular pressure (IOP) is a major risk factor for glaucoma; however, it is neither necessary nor sufficient for glaucomatous neurodegeneration, as patients can exhibit high IOP without developing glaucoma and patients can develop glaucoma with normal IOP. Yet FDA-approved treatment options are largely limited to approaches to minimize risk and reduce IOP. Thus, there is a critical need to target other aspects of glaucoma pathophysiology. Neuroinflammation is broadly defined here as immune-relevant responses, often involving microglia and astrocytes, within the central nervous system which may include peripheral immune cell infiltration. Burgeoning evidence has implicated glia in the development and progression of glaucoma in human tissues and mouse models. Most mouse models of glaucoma to date have shown that microglia and astrocytes are reactive in early stages of glaucomatous neurodegeneration prior to overt RGC loss. However, there is growing evidence that human and mouse glia adopt distinct phenotypes in response to neurodegeneration. Thus, there is critical need to expand our studies to include the new generations of human cell culture models. In this review, we discuss: 1) the evidence of neuroinflammatory processes in human glaucoma; 2) models of glaucoma relevant neuroinflammation; and the evidence specifically for 3) innate immune cell-driven and 4) macroglia-driven processes.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Correction: THBS1: a biomarker for PCOS and its role in pathogenesis via the PI3K/AKT signaling pathway. 更正：THBS1: PCOS的生物标志物及其通过PI3K/AKT信号通路在发病机制中的作用。

IF 2.6 4区生物学

Mammalian Genome Pub Date : 2026-06-25 DOI: 10.1007/s00335-026-10255-y

Jie Zhang, Luhongyuan Jin, Chi Chi, Wenjie Hou, Jinhua Zhou

引用次数: 0

Elucidating the therapeutic targets and multi-target mechanisms of salvianolic acid A for diabetic nephropathy. 丹酚酸A治疗糖尿病肾病的靶点及多靶点机制研究。

IF 2.6 4区生物学

Mammalian Genome Pub Date : 2026-06-24 DOI: 10.1007/s00335-026-10246-z

Tongfei Fu, Zhili Xiong, Hongwu Tao, Yongli Zhan

{"title":"Elucidating the therapeutic targets and multi-target mechanisms of salvianolic acid A for diabetic nephropathy.","authors":"Tongfei Fu, Zhili Xiong, Hongwu Tao, Yongli Zhan","doi":"10.1007/s00335-026-10246-z","DOIUrl":"https://doi.org/10.1007/s00335-026-10246-z","url":null,"abstract":"Diabetic nephropathy (DN) is a leading cause of chronic kidney disease. Salvianolic acid A (SAA) has shown promising therapeutic potential against DN, yet its underlying mechanisms and precise molecular targets remain incompletely elucidated. Potential targets of SAA were predicted using SwissTargetPrediction and SuperPred, with its drug-like properties evaluated by ADMET analysis. Diabetic nephropathy (DN)-related targets were collected from GEO, CTD, and GeneCards databases. Shared targets underwent GO and KEGG enrichment analyses. Core targets were identified through topological analysis in Cytoscape, machine learning, and Mendelian randomization validation. Molecular docking and dynamics simulations assessed the binding affinity and stability between SAA and core targets. Single-cell RNA sequencing data revealed their cell type-specific expression in kidney tissues. Experimental validation was performed using an in vitro high glucose-induced podocyte injury model analyzed by RT-qPCR. The intersection of 212 drug targets with 5,097 disease targets yielded 134 potential therapeutic targets for salvianolic acid A in DN. Machine learning and Mendelian randomization further identified eight targets with causal relationships to DN. Molecular docking demonstrated strong binding affinities of salvianolic acid A to the domains of FYN, AKR1B1, TNF, GALK1, HMGCR, MAP2K2, SCN4A, and ITGA5. Single-cell analysis revealed distinct expression patterns across different renal cell types. In vitro experiments demonstrated that SAA effectively protected podocytes from HG-induced injury. SAA alleviates diabetic nephropathy through multi-target mechanisms, influencing key genes involved in disease progression. This study provides a systematic elucidation of the therapeutic basis for SAA and supports its further clinical development.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

DeepDisSNP: Predicting disease-associated SNPs by representation learning on disease and SNP linkage disequilibrium networks. DeepDisSNP：通过疾病和SNP连锁不平衡网络的表示学习预测疾病相关SNP。

IF 2.6 4区生物学

Mammalian Genome Pub Date : 2026-06-19 DOI: 10.1007/s00335-026-10250-3

Duc-Hau Le

{"title":"DeepDisSNP: Predicting disease-associated SNPs by representation learning on disease and SNP linkage disequilibrium networks.","authors":"Duc-Hau Le","doi":"10.1007/s00335-026-10250-3","DOIUrl":"10.1007/s00335-026-10250-3","url":null,"abstract":"Genome-wide association studies (GWAS) have identified numerous disease-associated single nucleotide polymorphisms (SNPs), yet many potential disease-SNP associations remain undiscovered due to the high dimensionality and sparsity of genomic data. Computational approaches that integrate biological network information can complement existing GWAS resources by prioritizing candidate disease-associated SNPs for downstream investigation. In this study, we propose DeepDisSNP, a deep learning framework for disease-SNP association prediction that integrates disease similarity networks and chromosome-specific SNP linkage disequilibrium (LD) networks through graph attention network (GAT)-based representation learning. Disease similarity networks were constructed from MeSH-based disease relationships, while SNP LD networks were generated from Phase 1 and Phase 3 datasets of the 1000 Genomes Project under multiple LD thresholds. DeepDisSNP independently learns disease and SNP embeddings using weighted GAT encoders and subsequently predicts disease-SNP associations using a multilayer perceptron classifier. Extensive experiments across all 22 autosomal chromosomes demonstrated that DeepDisSNP consistently outperformed the state-of-the-art DisSNPNet framework under multiple experimental settings. Under the best-performing configuration, DeepDisSNP achieved AUROC and AUPRC values of approximately 0.96 and 0.95, respectively. Additional analyses demonstrated robustness across LD thresholds, 1000 Genomes Project phases, and increasingly imbalanced negative sampling settings. External GWAS resources, including NHGRI-EBI GWAS Catalog, PhenoScanner, and OpenGWAS, provided supportive biological evidence for many highly ranked predicted associations. Functional enrichment analyses further suggested biological relevance of the predicted SNP-associated genes. Overall, DeepDisSNP provides an effective network-based framework for large-scale disease-SNP association prioritization and may facilitate downstream genomic and translational research.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Correction: Are we fully exploiting genetic discoveries to understand and treat Alzheimer's disease? 纠正：我们是否充分利用基因发现来理解和治疗阿尔茨海默病？

IF 2.6 4区生物学

Mammalian Genome Pub Date : 2026-06-19 DOI: 10.1007/s00335-026-10247-y

Julie Williams

引用次数: 0

A comprehensive full-length transcriptome atlas across multiple organs of an Indian yak breed-Arunachali.

IF 2.6 4区生物学

Mammalian Genome Pub Date : 2026-06-18 DOI: 10.1007/s00335-026-10251-2

Martina Pukhrambam, Kishor U Tribhuvan, Atrayee Dutta, Vijay Paul, Avinash Pandey, Dinamani Medhi, Mokhtar Hussain, Shubham Loat, Vijai Pal Bhadana, Suresh Dabas, Joy Das, Vijay N Waghmare, A K Mohanty, Sujay Rakshit, Mihir Sarkar

{"title":"A comprehensive full-length transcriptome atlas across multiple organs of an Indian yak breed-Arunachali.","authors":"Martina Pukhrambam, Kishor U Tribhuvan, Atrayee Dutta, Vijay Paul, Avinash Pandey, Dinamani Medhi, Mokhtar Hussain, Shubham Loat, Vijai Pal Bhadana, Suresh Dabas, Joy Das, Vijay N Waghmare, A K Mohanty, Sujay Rakshit, Mihir Sarkar","doi":"10.1007/s00335-026-10251-2","DOIUrl":"https://doi.org/10.1007/s00335-026-10251-2","url":null,"abstract":"Yak (Bos grunniens) is a high-altitude adapted bovine species native to the Himalayan and Tibetan plateau, thriving at elevations above 3000 m from msl under hypobaric hypoxia. Despite its remarkable physiological adaptations, a complete transcriptomic understanding across multiple organs remains limited. In this study, full-length transcriptome sequencing of 22 tissues was performed using PacBio Iso-Seq, generating over 200,000 high-quality non-redundant RNA transcripts. This dataset significantly improves yak genome annotation and reveals widespread isoform diversity, including thousands of novel transcripts and 4,319 high-confidence lncRNAs. Enrichment of key hypoxia-related pathways such as HIF-1, PI3K-Akt, AMPK, and TGF-β was observed, along with tissue-specific expression patterns in vascular, immune, and reproductive systems. These results provide a valuable multi-organ transcriptomic resource and offer new insights into the genetic mechanisms supporting high-altitude adaptation in yak.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

The evolution of AI-integrated genome editing and its challenges. 人工智能整合基因组编辑的演变及其挑战。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2026-06-13 DOI: 10.1007/s00335-026-10248-x

Matthew Tze Jian Wong, Nur Diyana Zulkifli, Thurgashini Ravichandran, Kalidasan Vasodavan, Osama Al-Shaibah, Galib Muhammad Shahriar Himel, Anusha Achuthan, Mohana Anita Anthonysamy, Kumitaa Theva Das

{"title":"The evolution of AI-integrated genome editing and its challenges.","authors":"Matthew Tze Jian Wong, Nur Diyana Zulkifli, Thurgashini Ravichandran, Kalidasan Vasodavan, Osama Al-Shaibah, Galib Muhammad Shahriar Himel, Anusha Achuthan, Mohana Anita Anthonysamy, Kumitaa Theva Das","doi":"10.1007/s00335-026-10248-x","DOIUrl":"https://doi.org/10.1007/s00335-026-10248-x","url":null,"abstract":"Artificial Intelligence (AI) is poised to revolutionize the field of genome editing by enhancing precision, efficiency, and accessibility. AI-driven approaches are already improving the design of CRISPR-based systems by enabling more accurate identification of target sequences and predicting off-target effects. Machine learning (ML) algorithms can analyze vast genomic data, as well as identify patterns and mutations that might be overlooked by traditional methods. Taking together, utilizing AI/ML tools allow for the enhancement of every step in genome editing. Recent advances also demonstrated that AI-powered tools can facilitate the simulation and modeling of genetic modifications, predicting their effects on cellular behavior and phenotypes. This allows for a more rapid prediction of the genome editing effects, without the need for wet lab. Additionally, AI can accelerate drug discovery and therapeutic development by streamlining the identification of genetic targets and optimizing gene therapies. The integration of AI with genome editing promises to democratize access to cutting-edge technologies, enabling researchers to design and plan for complex genetic modifications with minimal technical expertise. Drawing from various examples, this paper dives into the advancements and applications of AI in genome editing, its limitations, as well as future directions and opportunities in this field.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Detection of a complex chromosomal rearrangement in a novel mouse mutant by optical genome mapping. 利用光学基因组作图技术检测一种新型小鼠突变体的复杂染色体重排。

IF 2.6 4区生物学

Mammalian Genome Pub Date : 2026-06-13 DOI: 10.1007/s00335-026-10241-4

Gretchen Holtgrefe, Patricia A Wight

{"title":"Detection of a complex chromosomal rearrangement in a novel mouse mutant by optical genome mapping.","authors":"Gretchen Holtgrefe, Patricia A Wight","doi":"10.1007/s00335-026-10241-4","DOIUrl":"10.1007/s00335-026-10241-4","url":null,"abstract":"Here we highlight the utilities of optical genome mapping (OGM) in determining the genomic rearrangements present in a novel transgenic mouse line (Line 781), which expresses the bacterial lacZ reporter gene under control of the mouse myelin proteolipid protein (Plp1) promoter. Hemizygous transgenic mice from Line 781 present with a mutant phenotype (documented here) which entails small body size and paws and craniofacial aberrations that are 100% penetrant, whereas their non-transgenic littermates are phenotypically normal. OGM was used to determine that the transgene sits at the intersection of an unbalanced reciprocal translocation between chromosomes 1 and 2, with deletion of approximately 3.9 (chr1) and 1.8 (chr2) Mbp from the rearranged (derivative) chromosomes, thus resulting in a monosomy over these regions in the mutant genome. As well, OGM was able to determine the number of full-length copies of transgene that integrated and their orientation. Sanger sequencing of PCR products that span a junction were used to determine the chromosomal breakpoints and transgene integration site, precisely. The complex chromosomal rearrangements in Line 781 span 38 protein-coding genes that result in the transection of 1 gene from chr1 and deletion of 33 and 4 genes from chr1 and chr2, respectively. The resulting mutant phenotype is consistent with 1q24 deletion syndrome in humans having an interstitial deletion of the syntenic region in Chr1. Thus, our mouse mutant may serve as an animal model, in future studies, to explore the molecular and cellular basis of anomalies present in patients with 1q24 deletion syndrome.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

A novel biological function-based method for mining core genes in rare disease with limited cases. 一种基于生物学功能的新方法挖掘罕见病有限病例的核心基因。

IF 2.7 4区生物学

Mammalian Genome Pub Date : 2026-06-12 DOI: 10.1007/s00335-026-10249-w

Yongqiang Gong, Kailong Zhao, Xicheng Wang, Xi Peng, Yin Liu

{"title":"A novel biological function-based method for mining core genes in rare disease with limited cases.","authors":"Yongqiang Gong, Kailong Zhao, Xicheng Wang, Xi Peng, Yin Liu","doi":"10.1007/s00335-026-10249-w","DOIUrl":"10.1007/s00335-026-10249-w","url":null,"abstract":"Conventional high - throughput sequencing data analysis methods, relying on large cohorts, are unsuitable for rare diseases with few cases and poor at explaining gene biological functions. This study proposes a biological-function-based method for mining core genes under limited-sample conditions. Using colorectal cancer (CRC) and its rare subtype signet-ring cell carcinoma (SRCC) as examples, differential expression analysis was performed separately for each SRCC sample against CRC samples. Shared genes obtained through progressive intersections were defined as the initial core gene set (List 1). Non-core genes were subjected to functional enrichment analysis, and pathway-associated genes were integrated to construct the non-core gene set. Two independent SRCC samples were subsequently used for secondary mining to obtain the final biologically significant core gene set (List 2). In addition, RankProd (RP), Robust Rank Aggregation (RRA), and an external mucinous adenocarcinoma dataset (GSE281917) were used for validation. First-round mining identified 246 core genes in SRCC, while secondary mining generated 66 and 65 biologically significant core genes from two validation samples with a high degree of overlap. RP identified 1,850 candidate genes and RRA identified 601 candidate genes, among which 64 genes overlapped with the 65 genes identified by this method. In the external mucinous adenocarcinoma dataset, first-round mining identified 144 core genes, while secondary mining generated 122 and 119 core genes with high overlap between validation samples. This method enables the identification of biologically significant core genes in rare diseases under limited-sample conditions, improves the biological interpretability of gene-mining results, demonstrates stable performance in both SRCC and external mucinous adenocarcinoma datasets, and provides a reliable experimental basis for the advancement of precision medicine in rare disease research.","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148226240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Cell therapy for age-related macular degeneration. 年龄相关性黄斑变性的细胞治疗。

IF 2.6 4区生物学

Mammalian Genome Pub Date : 2026-05-28 DOI: 10.1007/s00335-026-10242-3

Affan Shaikh, Martin F Pera

引用次数: 0