{"title":"Advances in integrating single-cell sequencing data to unravel the mechanism of ferroptosis in cancer.","authors":"Zhaolan Du, Yi Shi, Jianjun Tan","doi":"10.1093/bfgp/elae025","DOIUrl":"https://doi.org/10.1093/bfgp/elae025","url":null,"abstract":"<p><p>Ferroptosis, a commonly observed type of programmed cell death caused by abnormal metabolic and biochemical mechanisms, is frequently triggered by cellular stress. The occurrence of ferroptosis is predominantly linked to pathophysiological conditions due to the substantial impact of various metabolic pathways, including fatty acid metabolism and iron regulation, on cellular reactions to lipid peroxidation and ferroptosis. This mode of cell death serves as a fundamental factor in the development of numerous diseases, thereby presenting a range of therapeutic targets. Single-cell sequencing technology provides insights into the cellular and molecular characteristics of individual cells, as opposed to bulk sequencing, which provides data in a more generalized manner. Single-cell sequencing has found extensive application in the field of cancer research. This paper reviews the progress made in ferroptosis-associated cancer research using single-cell sequencing, including ferroptosis-associated pathways, immune checkpoints, biomarkers, and the identification of cell clusters associated with ferroptosis in tumors. In general, the utilization of single-cell sequencing technology has the potential to contribute significantly to the investigation of the mechanistic regulatory pathways linked to ferroptosis. Moreover, it can shed light on the intricate connection between ferroptosis and cancer. This technology holds great promise in advancing tumor-wide diagnosis, targeted therapy, and prognosis prediction.</p>","PeriodicalId":55323,"journal":{"name":"Briefings in Functional Genomics","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"AMLdb: a comprehensive multi-omics platform to identify biomarkers and drug targets for acute myeloid leukemia.","authors":"Keerthana Vinod Kumar, Ambuj Kumar, Kavita Kundal, Avik Sengupta, Kunjulakshmi R, Subashani Singh, Bhanu Teja Korra, Simran Sharma, Vandana Suresh, Mayilaadumveettil Nishana, Rahul Kumar","doi":"10.1093/bfgp/elae024","DOIUrl":"https://doi.org/10.1093/bfgp/elae024","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is one of the leading leukemic malignancies in adults. The heterogeneity of the disease makes the diagnosis and treatment extremely difficult. With the advent of next-generation sequencing (NGS) technologies, exploration at the molecular level for the identification of biomarkers and drug targets has been the focus for the researchers to come up with novel therapies for better prognosis and survival outcomes of AML patients. However, the huge amount of data from NGS platforms requires a comprehensive AML platform to streamline literature mining efforts and save time. To facilitate this, we developed AMLdb, an interactive multi-omics platform that allows users to query, visualize, retrieve, and analyse AML related multi-omics data. AMLdb contains 86 datasets for gene expression profiles, 15 datasets for methylation profiles, CRISPR-Cas9 knockout screens of 26 AML cell lines, sensitivity of 26 AML cell lines to 288 drugs, mutations in 41 unique genes in 23 AML cell lines, and information on 41 experimentally validated biomarkers. In this study, we have reported five genes, i.e. CBFB, ENO1, IMPDH2, SEPHS2, and MYH9 identified via our analysis using AMLdb. ENO1 is uniquely identified gene which requires further investigation as a novel potential target while other reported genes have been previously confirmed as targets through experimental studies. Top of form we believe that these findings utilizing AMLdb can make it an invaluable resource to accelerate the development of effective therapies for AML and assisting the research community in advancing their understanding of AML pathogenesis. AMLdb is freely available at https://project.iith.ac.in/cgntlab/amldb.</p>","PeriodicalId":55323,"journal":{"name":"Briefings in Functional Genomics","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A comprehensive survey of dimensionality reduction and clustering methods for single-cell and spatial transcriptomics data.","authors":"Yidi Sun, Lingling Kong, Jiayi Huang, Hongyan Deng, Xinling Bian, Xingfeng Li, Feifei Cui, Lijun Dou, Chen Cao, Quan Zou, Zilong Zhang","doi":"10.1093/bfgp/elae023","DOIUrl":"https://doi.org/10.1093/bfgp/elae023","url":null,"abstract":"<p><p>In recent years, the application of single-cell transcriptomics and spatial transcriptomics analysis techniques has become increasingly widespread. Whether dealing with single-cell transcriptomic or spatial transcriptomic data, dimensionality reduction and clustering are indispensable. Both single-cell and spatial transcriptomic data are often high-dimensional, making the analysis and visualization of such data challenging. Through dimensionality reduction, it becomes possible to visualize the data in a lower-dimensional space, allowing for the observation of relationships and differences between cell subpopulations. Clustering enables the grouping of similar cells into the same cluster, aiding in the identification of distinct cell subpopulations and revealing cellular diversity, providing guidance for downstream analyses. In this review, we systematically summarized the most widely recognized algorithms employed for the dimensionality reduction and clustering analysis of single-cell transcriptomic and spatial transcriptomic data. This endeavor provides valuable insights and ideas that can contribute to the development of novel tools in this rapidly evolving field.</p>","PeriodicalId":55323,"journal":{"name":"Briefings in Functional Genomics","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keyu Wan, Tiantian Nie, Wenhao Ouyang, Yunjing Xiong, Jing Bian, Ying Huang, Li Ling, Zhenjun Huang, Xianhua Zhu
{"title":"Exploring the impact of N4-acetylcytidine modification in RNA on non-neoplastic disease: unveiling its role in pathogenesis and therapeutic opportunities.","authors":"Keyu Wan, Tiantian Nie, Wenhao Ouyang, Yunjing Xiong, Jing Bian, Ying Huang, Li Ling, Zhenjun Huang, Xianhua Zhu","doi":"10.1093/bfgp/elae020","DOIUrl":"https://doi.org/10.1093/bfgp/elae020","url":null,"abstract":"<p><p>RNA modifications include not only methylation modifications, such as m6A, but also acetylation modifications, which constitute a complex interaction involving \"writers,\" \"readers,\" and \"erasers\" that play crucial roles in growth, genetics, and disease. N4-acetylcytidine (ac4C) is an ancient and highly conserved RNA modification that plays a profound role in the pathogenesis of a wide range of diseases. This review provides insights into the functional impact of ac4C modifications in disease and introduces new perspectives for disease treatment. These studies provide important insights into the biological functions of post-transcriptional RNA modifications and their potential roles in disease mechanisms, offering new perspectives and strategies for disease treatment.</p>","PeriodicalId":55323,"journal":{"name":"Briefings in Functional Genomics","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141263641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sesame Genomic Web Resource (SesameGWR): a well-annotated data resource for transcriptomic signatures of abiotic and biotic stress responses in sesame (Sesamum indicum L.).","authors":"Himanshu Avashthi, Ulavappa Basavanneppa Angadi, Divya Chauhan, Anuj Kumar, Dwijesh Chandra Mishra, Parimalan Rangan, Rashmi Yadav, Dinesh Kumar","doi":"10.1093/bfgp/elae022","DOIUrl":"https://doi.org/10.1093/bfgp/elae022","url":null,"abstract":"<p><p>Sesame (Sesamum indicum L.) is a globally cultivated oilseed crop renowned for its historical significance and widespread growth in tropical and subtropical regions. With notable nutritional and medicinal attributes, sesame has shown promising effects in combating malnutrition cancer, diabetes, and other diseases like cardiovascular problems. However, sesame production faces significant challenges from environmental threats such as charcoal rot, drought, salinity, and waterlogging stress, resulting in economic losses for farmers. The scarcity of information on stress-resistance genes and pathways exacerbates these challenges. Despite its immense importance, there is currently no platform available to provide comprehensive information on sesame, which significantly hinders the mining of various stress-associated genes and the molecular breeding of sesame. To address this gap, here a free, web-accessible, and user-friendly genomic web resource (SesameGWR, http://backlin.cabgrid.res.in/sesameGWR/) has been developed This platform provides key insights into differentially expressed genes, transcription factors, miRNAs, and molecular markers like simple sequence repeats, single nucleotide polymorphisms, and insertions and deletions associated with both biotic and abiotic stresses.. The functional genomics information and annotations embedded in this web resource were predicted through RNA-seq data analysis. Considering the impact of climate change and the nutritional and medicinal importance of sesame, this study is of utmost importance in understanding stress responses. SesameGWR will serve as a valuable tool for developing climate-resilient sesame varieties, thereby enhancing the productivity of this ancient oilseed crop.</p>","PeriodicalId":55323,"journal":{"name":"Briefings in Functional Genomics","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Predicting gastric cancer tumor mutational burden from histopathological images using multimodal deep learning.","authors":"Jing Li, Haiyan Liu, Wei Liu, Peijun Zong, Kaimei Huang, Zibo Li, Haigang Li, Ting Xiong, Geng Tian, Chun Li, Jialiang Yang","doi":"10.1093/bfgp/elad032","DOIUrl":"10.1093/bfgp/elad032","url":null,"abstract":"<p><p>Tumor mutational burden (TMB) is a significant predictive biomarker for selecting patients that may benefit from immune checkpoint inhibitor therapy. Whole exome sequencing is a common method for measuring TMB; however, its clinical application is limited by the high cost and time-consuming wet-laboratory experiments and bioinformatics analysis. To address this challenge, we downloaded multimodal data of 326 gastric cancer patients from The Cancer Genome Atlas, including histopathological images, clinical data and various molecular data. Using these data, we conducted a comprehensive analysis to investigate the relationship between TMB, clinical factors, gene expression and image features extracted from hematoxylin and eosin images. We further explored the feasibility of predicting TMB levels, i.e. high and low TMB, by utilizing a residual network (Resnet)-based deep learning algorithm for histopathological image analysis. Moreover, we developed a multimodal fusion deep learning model that combines histopathological images with omics data to predict TMB levels. We evaluated the performance of our models against various state-of-the-art methods using different TMB thresholds and obtained promising results. Specifically, our histopathological image analysis model achieved an area under curve (AUC) of 0.749. Notably, the multimodal fusion model significantly outperformed the model that relied only on histopathological images, with the highest AUC of 0.971. Our findings suggest that histopathological images could be used with reasonable accuracy to predict TMB levels in gastric cancer patients, while multimodal deep learning could achieve even higher levels of accuracy. This study sheds new light on predicting TMB in gastric cancer patients.</p>","PeriodicalId":55323,"journal":{"name":"Briefings in Functional Genomics","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9965530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Omics-based deep learning approaches for lung cancer decision-making and therapeutics development.","authors":"Thi-Oanh Tran, Thanh Hoa Vo, Nguyen Quoc Khanh Le","doi":"10.1093/bfgp/elad031","DOIUrl":"10.1093/bfgp/elad031","url":null,"abstract":"<p><p>Lung cancer has been the most common and the leading cause of cancer deaths globally. Besides clinicopathological observations and traditional molecular tests, the advent of robust and scalable techniques for nucleic acid analysis has revolutionized biological research and medicinal practice in lung cancer treatment. In response to the demands for minimally invasive procedures and technology development over the past decade, many types of multi-omics data at various genome levels have been generated. As omics data grow, artificial intelligence models, particularly deep learning, are prominent in developing more rapid and effective methods to potentially improve lung cancer patient diagnosis, prognosis and treatment strategy. This decade has seen genome-based deep learning models thriving in various lung cancer tasks, including cancer prediction, subtype classification, prognosis estimation, cancer molecular signatures identification, treatment response prediction and biomarker development. In this study, we summarized available data sources for deep-learning-based lung cancer mining and provided an update on recent deep learning models in lung cancer genomics. Subsequently, we reviewed the current issues and discussed future research directions of deep-learning-based lung cancer genomics research.</p>","PeriodicalId":55323,"journal":{"name":"Briefings in Functional Genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10281428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Pan, Yueying Gao, Gang Xu, Lei Yu, Qi Xu, Jinyang Yu, Meng Liu, Can Zhang, Yanlin Ma, Yongsheng Li
{"title":"Widespread transcriptomic alterations of transient receptor potential channel genes in cancer.","authors":"Tao Pan, Yueying Gao, Gang Xu, Lei Yu, Qi Xu, Jinyang Yu, Meng Liu, Can Zhang, Yanlin Ma, Yongsheng Li","doi":"10.1093/bfgp/elad023","DOIUrl":"10.1093/bfgp/elad023","url":null,"abstract":"<p><p>Ion channels, in particular transient-receptor potential (TRP) channels, are essential genes that play important roles in many physiological processes. Emerging evidence has demonstrated that TRP genes are involved in a number of diseases, including various cancer types. However, we still lack knowledge about the expression alterations landscape of TRP genes across cancer types. In this review, we comprehensively reviewed and summarised the transcriptomes from more than 10 000 samples in 33 cancer types. We found that TRP genes were widespreadly transcriptomic dysregulated in cancer, which was associated with clinical survival of cancer patients. Perturbations of TRP genes were associated with a number of cancer pathways across cancer types. Moreover, we reviewed the functions of TRP family gene alterations in a number of diseases reported in recent studies. Taken together, our study comprehensively reviewed TRP genes with extensive transcriptomic alterations and their functions will directly contribute to cancer therapy and precision medicine.</p>","PeriodicalId":55323,"journal":{"name":"Briefings in Functional Genomics","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9948253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Akhil Kumar, Rishika Kaushal, Himanshi Sharma, Khushboo Sharma, Manoj B Menon, Vivekanandan P
{"title":"Mapping of long stretches of highly conserved sequences in over 6 million SARS-CoV-2 genomes.","authors":"Akhil Kumar, Rishika Kaushal, Himanshi Sharma, Khushboo Sharma, Manoj B Menon, Vivekanandan P","doi":"10.1093/bfgp/elad027","DOIUrl":"10.1093/bfgp/elad027","url":null,"abstract":"<p><p>We identified 11 conserved stretches in over 6.3 million SARS-CoV-2 genomes including all the major variants of concerns. Each conserved stretch is ≥100 nucleotides in length with ≥99.9% conservation at each nucleotide position. Interestingly, six of the eight conserved stretches in ORF1ab overlapped significantly with well-folded experimentally verified RNA secondary structures. Furthermore, two of the conserved stretches were mapped to regions within the S2-subunit that undergo dynamic structural rearrangements during viral fusion. In addition, the conserved stretches were significantly depleted for zinc-finger antiviral protein (ZAP) binding sites, which facilitated the recognition and degradation of viral RNA. These highly conserved stretches in the SARS-CoV-2 genome were poorly conserved at the nucleotide level among closely related β-coronaviruses, thus representing ideal targets for highly specific and discriminatory diagnostic assays. Our findings highlight the role of structural constraints at both RNA and protein levels that contribute to the sequence conservation of specific genomic regions in SARS-CoV-2.</p>","PeriodicalId":55323,"journal":{"name":"Briefings in Functional Genomics","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9824704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue-Chao Li, Zhu-Hong You, Chang-Qing Yu, Lei Wang, Lun Hu, Peng-Wei Hu, Yan Qiao, Xin-Fei Wang, Yu-An Huang
{"title":"DeepCMI: a graph-based model for accurate prediction of circRNA-miRNA interactions with multiple information.","authors":"Yue-Chao Li, Zhu-Hong You, Chang-Qing Yu, Lei Wang, Lun Hu, Peng-Wei Hu, Yan Qiao, Xin-Fei Wang, Yu-An Huang","doi":"10.1093/bfgp/elad030","DOIUrl":"10.1093/bfgp/elad030","url":null,"abstract":"<p><p>Recently, the role of competing endogenous RNAs in regulating gene expression through the interaction of microRNAs has been closely associated with the expression of circular RNAs (circRNAs) in various biological processes such as reproduction and apoptosis. While the number of confirmed circRNA-miRNA interactions (CMIs) continues to increase, the conventional in vitro approaches for discovery are expensive, labor intensive, and time consuming. Therefore, there is an urgent need for effective prediction of potential CMIs through appropriate data modeling and prediction based on known information. In this study, we proposed a novel model, called DeepCMI, that utilizes multi-source information on circRNA/miRNA to predict potential CMIs. Comprehensive evaluations on the CMI-9905 and CMI-9589 datasets demonstrated that DeepCMI successfully infers potential CMIs. Specifically, DeepCMI achieved AUC values of 90.54% and 94.8% on the CMI-9905 and CMI-9589 datasets, respectively. These results suggest that DeepCMI is an effective model for predicting potential CMIs and has the potential to significantly reduce the need for downstream in vitro studies. To facilitate the use of our trained model and data, we have constructed a computational platform, which is available at http://120.77.11.78/DeepCMI/. The source code and datasets used in this work are available at https://github.com/LiYuechao1998/DeepCMI.</p>","PeriodicalId":55323,"journal":{"name":"Briefings in Functional Genomics","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}