Genomics & informatics最新文献

Single-cell network biology enabling cell-type-resolved disease genetics.

Genomics & informatics Pub Date : 2025-03-27 DOI: 10.1186/s44342-025-00042-7

Junha Cha, Insuk Lee

{"title":"Single-cell network biology enabling cell-type-resolved disease genetics.","authors":"Junha Cha, Insuk Lee","doi":"10.1186/s44342-025-00042-7","DOIUrl":"10.1186/s44342-025-00042-7","url":null,"abstract":"Gene network models provide a foundation for graph theory approaches, aiding in the novel discovery of drug targets, disease genes, and genetic mechanisms for various biological functions. Disease genetics must be interpreted within the cellular context of disease-associated cell types, which cannot be achieved with datasets consisting solely of organism-level samples. Single-cell RNA sequencing (scRNA-seq) technology allows computational distinction of cell states which provides a unique opportunity to understand cellular biology that drives disease processes. Importantly, the abundance of cell samples with their transcriptome-wide profile allows the modeling of systemic cell-type-specific gene networks (CGNs), offering insights into gene-cell-disease relationships. In this review, we present reference-based and de novo inference of gene functional interaction networks that we have recently developed using scRNA-seq datasets. We also introduce a compendium of CGNs as a useful resource for cell-type-resolved disease genetics. By leveraging these advances, we envision single-cell network biology as the key approach for mapping the gene-cell-disease axis.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"23 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial for the special collection: frontiers in rare disease genetics. 专集编辑：罕见病遗传学前沿。

Genomics & informatics Pub Date : 2025-03-07 DOI: 10.1186/s44342-025-00039-2

Murim Choi

引用次数: 0

Impact of cysteine mutations on the structural dynamics and functional impairment of SOD1: insights into the pathogenicity of amyotrophic lateral sclerosis.

Genomics & informatics Pub Date : 2025-03-06 DOI: 10.1186/s44342-025-00041-8

Jessica Jeejan, Lawanya Rao, Shivank Sadasivan, Richa Lopes, Norine Dsouza

{"title":"Impact of cysteine mutations on the structural dynamics and functional impairment of SOD1: insights into the pathogenicity of amyotrophic lateral sclerosis.","authors":"Jessica Jeejan, Lawanya Rao, Shivank Sadasivan, Richa Lopes, Norine Dsouza","doi":"10.1186/s44342-025-00041-8","DOIUrl":"10.1186/s44342-025-00041-8","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease prevalent in American and European populations, with its onset and progression significantly influenced by mutations in the superoxide dismutase 1 (SOD1) protein. While previous studies have highlighted the effects of mutations in the metal-binding region and catalytic region and dimerisation of SOD1, the impact of mutations involving the Cysteine residue at the N-terminal end remains unexplored. This study investigates the effects of Cysteine-to-Trp, Phe, Ser, and Gly mutations at the 6th position of SOD1's N-terminal end on its structural dynamics and functional impairment. Our computational analysis using PolyPhen-2, PROVEAN, Meta-SNP, and PhD-SNP predicted mutations to be deleterious, with their negative impacts likely contributing to disease development. Furthermore, stability studies and bonding pattern changes due to the mutations, analysed by mCSM, SDM, DUET, Dynamut2, and PremPS revealed changes in free energy and disruption in intramolecular interactions. The molecular dynamics studies revealed distinct changes in stability patterns among the mutations, particularly in Cys6Trp and Cys6Phe. All the mutations primarily altered the catalytic region of the protein; additionally, Cys6Phe and Cys6Gly caused disruption in the metal-binding region. The impact of mutations on the dimerisation of SOD1, analysed using MM/PBSA showed destabilisation due to Cys6Phe mutation. These findings provide molecular insights into the clinical symptoms observed in patients, highlighting the critical impact of the Cys6Phe mutation on the metal-binding and catalytic loops of SOD1 along with destabilisation of dimer formation. Overall, our analysis offers valuable insights into the molecular mechanisms driving structural changes in SOD1 due to mutations, contributing to a deeper understanding of their role in ALS pathogenicity.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"23 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lessons from national biobank projects utilizing whole-genome sequencing for population-scale genomics.

Genomics & informatics Pub Date : 2025-03-06 DOI: 10.1186/s44342-025-00040-9

Hyeji Lee, Wooheon Kim, Nahyeon Kwon, Chanhee Kim, Sungmin Kim, Joon-Yong An

{"title":"Lessons from national biobank projects utilizing whole-genome sequencing for population-scale genomics.","authors":"Hyeji Lee, Wooheon Kim, Nahyeon Kwon, Chanhee Kim, Sungmin Kim, Joon-Yong An","doi":"10.1186/s44342-025-00040-9","DOIUrl":"10.1186/s44342-025-00040-9","url":null,"abstract":"Large-scale national biobank projects utilizing whole-genome sequencing have emerged as transformative resources for understanding human genetic variation and its relationship to health and disease. These initiatives, which include the UK Biobank, All of Us Research Program, Singapore's PRECISE, Biobank Japan, and the National Project of Bio-Big Data of Korea, are generating unprecedented volumes of high-resolution genomic data integrated with comprehensive phenotypic, environmental, and clinical information. This review examines the methodologies, contributions, and challenges of major WGS-based national genome projects worldwide. We first discuss the landscape of national biobank initiatives, highlighting their distinct approaches to data collection, participant recruitment, and phenotype characterization. We then introduce recent technological advances that enable efficient processing and analysis of large-scale WGS data, including improvements in variant calling algorithms, innovative methods for creating multi-sample VCFs, optimized data storage formats, and cloud-based computing solutions. The review synthesizes key discoveries from these projects, particularly in identifying expression quantitative trait loci and rare variants associated with complex diseases. Our review introduces the latest findings from the National Project of Bio-Big Data of Korea, which has advanced our understanding of population-specific genetic variation and rare diseases in Korean and East Asian populations. Finally, we discuss future directions and challenges in maximizing the impact of these resources on precision medicine and global health equity. This comprehensive examination demonstrates how large-scale national genome projects are revolutionizing genetic research and healthcare delivery while highlighting the importance of continued investment in diverse, population-specific genomic resources.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"23 1","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comprehensive Analysis of TCR and BCR Repertoires: Insights into Methodologies, Challenges, and Applications.

Genomics & informatics Pub Date : 2025-02-24 DOI: 10.1186/s44342-024-00034-z

Kayoung Seo, Jung Kyoon Choi

引用次数: 0

Deciphering single-cell genomic architecture: insights into cellular heterogeneity and regulatory dynamics.

Genomics & informatics Pub Date : 2025-02-11 DOI: 10.1186/s44342-025-00037-4

Byunghee Kang, Hyeonji Lee, Tae-Young Roh

{"title":"Deciphering single-cell genomic architecture: insights into cellular heterogeneity and regulatory dynamics.","authors":"Byunghee Kang, Hyeonji Lee, Tae-Young Roh","doi":"10.1186/s44342-025-00037-4","DOIUrl":"10.1186/s44342-025-00037-4","url":null,"abstract":"Background: The genomic architecture of eukaryotes exhibits dynamic spatial and temporal changes, enabling cellular processes critical for maintaining viability and functional diversity. Recent advances in sequencing technologies have facilitated the dissection of genomic architecture and functional activity at single-cell resolution, moving beyond the averaged signals typically derived from bulk cell analyses.Main body: The advent of single-cell genomics and epigenomics has yielded transformative insights into cellular heterogeneity, behavior, and biological complexity with unparalleled genomic resolution and reproducibility. This review summarizes recent progress in the characterization of genomic architecture at the single-cell level, emphasizing the impact of structural variation and chromatin organization on gene regulatory networks and cellular identity.Conclusion: Future directions in single-cell genomics and high-resolution epigenomic methodologies are explored, focusing on emerging challenges and potential impacts on the understanding of cellular states, regulatory dynamics, and the intricate mechanisms driving cellular function and diversity. Future perspectives on the challenges and potential implications of single-cell genomics, along with high-resolution genomic and epigenomic technologies for understanding cellular states and regulatory dynamics, are also discussed.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"23 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic regulation of angiogenesis and its therapeutics.

Genomics & informatics Pub Date : 2025-02-11 DOI: 10.1186/s44342-025-00038-3

Dong Kyu Choi

{"title":"Epigenetic regulation of angiogenesis and its therapeutics.","authors":"Dong Kyu Choi","doi":"10.1186/s44342-025-00038-3","DOIUrl":"10.1186/s44342-025-00038-3","url":null,"abstract":"Angiogenesis, the formation of new blood vessels from preexisting ones, is essential for normal development, wound healing, and tissue repair. However, dysregulated angiogenesis is implicated in various pathological conditions, including cancer, diabetic retinopathy, and atherosclerosis. Epigenetic modifications, including DNA methylation, histone modification, and noncoding RNAs (e.g., miRNAs), play a crucial role in regulating angiogenic gene expression without altering the underlying DNA sequence. These modifications tightly regulate the balance between pro-angiogenic and anti-angiogenic factors, thereby influencing endothelial cell proliferation, migration, and tube formation. In recent years, epigenetic drugs, such as DNA methyltransferase inhibitors (e.g., azacitidine, decitabine), histone deacetylase inhibitors (e.g., vorinostat, romidepsin), and BET inhibitors (e.g., JQ1), have emerged as promising therapeutic strategies for targeting abnormal angiogenesis. These agents modulate gene expression patterns, reactivating silenced tumor suppressor genes while downregulating pro-angiogenic signaling pathways. Additionally, miRNA modulators, such as MRG-110 and MRG-201, provide precise regulation of angiogenesis-related pathways, demonstrating significant therapeutic potential in preclinical models. This review underscores the intricate interplay between epigenetic regulation and angiogenesis, highlighting key mechanisms and therapeutic applications. Advancing our understanding of these processes will enable the development of more effective and targeted epigenetic therapies for angiogenesis-related diseases, paving the way for innovative clinical interventions.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"23 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative analysis of generative LLMs for labeling entities in clinical notes.

Genomics & informatics Pub Date : 2025-02-06 DOI: 10.1186/s44342-024-00036-x

Rodrigo Del Moral-González, Helena Gómez-Adorno, Orlando Ramos-Flores

引用次数: 0

Analyzing COVID-19 progression with Markov multistage models: insights from a Korean cohort.

Genomics & informatics Pub Date : 2025-01-27 DOI: 10.1186/s44342-024-00035-y

Frank Aimee Rodrigue Ndagijimana, Taesung Park

{"title":"Analyzing COVID-19 progression with Markov multistage models: insights from a Korean cohort.","authors":"Frank Aimee Rodrigue Ndagijimana, Taesung Park","doi":"10.1186/s44342-024-00035-y","DOIUrl":"10.1186/s44342-024-00035-y","url":null,"abstract":"Background: Understanding the progression and recovery process of COVID-19 is crucial for guiding public health strategies and developing targeted interventions. This longitudinal cohort study aims to elucidate the dynamics of COVID-19 severity progression and evaluate the impact of underlying health conditions on these transitions, providing critical insights for more effective disease management.Methods: Data from 4549 COVID-19 patients admitted to Seoul National University Boramae Medical Center between February 5th, 2020, and October 30th, 2021, were analyzed using a 5-state continuous-time Markov multistate model. The model estimated instantaneous transition rates between different levels of COVID-19 severity, predicted probabilities of state transitions, and determined hazard ratios associated with underlying comorbidities.Results: The analysis revealed that most patients stabilized in their initial state, with 72.2% of patients with moderate symptoms remaining moderate. Patients with hypertension had a 67.6% higher risk of progressing from moderate to severe, while those with diabetes had an 89.9% higher risk of deteriorating from severe to critical. Although transition rates to death were low early in hospitalization, these comorbidities significantly increased the likelihood of worsening conditions.Conclusion: This study highlights the utility of continuous-time Markov multistate models in assessing COVID-19 severity progression among hospitalized patients. The findings indicate that patients are more likely to recover than to experience worsening conditions. However, hypertension and diabetes significantly increase the risk of severe outcomes, underscoring the importance of managing these conditions in COVID-19 patients.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"23 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural insights into antibody-based immunotherapy for hepatocellular carcinoma. 基于抗体的肝细胞癌免疫治疗的结构见解。

Genomics & informatics Pub Date : 2025-01-20 DOI: 10.1186/s44342-024-00033-0

Masaud Shah, Muhammad Hussain, Hyun Goo Woo

{"title":"Structural insights into antibody-based immunotherapy for hepatocellular carcinoma.","authors":"Masaud Shah, Muhammad Hussain, Hyun Goo Woo","doi":"10.1186/s44342-024-00033-0","DOIUrl":"10.1186/s44342-024-00033-0","url":null,"abstract":"Hepatocellular carcinoma (HCC) is one of the most common types of primary liver cancer and remains a leading cause of cancer-related deaths worldwide. While traditional approaches like surgical resection and tyrosine kinase inhibitors struggle against the tumor's immune evasion, monoclonal antibody (mAb)-based immunotherapies have emerged as promising alternatives. Several therapeutic antibodies that counter the immunosuppressive tumor microenvironment have demonstrated efficacy in clinical trials, leading to FDA approvals for advanced HCC treatment. A crucial aspect of advancing these therapies lies in understanding the structural interactions between antibodies and their targets. Recent findings indicate that mAbs and bispecific antibodies (bsAbs) can target different, non-overlapping epitopes on immune checkpoints such as PD-1 and CTLA-4. This review delves into the epitope-paratope interactions of structurally unresolved mAbs and bsAbs, and discusses the potential for combination therapies based on their non-overlapping epitopes. By leveraging this unique feature, combination therapies could enhance immune activation, reduce resistance, and improve overall efficacy, marking a new direction for antibody-based immunotherapy in HCC.","PeriodicalId":94288,"journal":{"name":"Genomics & informatics","volume":"23 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0