{"title":"Developing ChatGPT for biology and medicine: a complete review of biomedical question answering.","authors":"Qing Li, Lei Li, Yu Li","doi":"10.52601/bpr.2024.240004","DOIUrl":"10.52601/bpr.2024.240004","url":null,"abstract":"<p><p>ChatGPT explores a strategic blueprint of question answering (QA) to deliver medical diagnoses, treatment recommendations, and other healthcare support. This is achieved through the increasing incorporation of medical domain data via natural language processing (NLP) and multimodal paradigms. By transitioning the distribution of text, images, videos, and other modalities from the general domain to the medical domain, these techniques have accelerated the progress of medical domain question answering (MDQA). They bridge the gap between human natural language and sophisticated medical domain knowledge or expert-provided manual annotations, handling large-scale, diverse, unbalanced, or even unlabeled data analysis scenarios in medical contexts. Central to our focus is the utilization of language models and multimodal paradigms for medical question answering, aiming to guide the research community in selecting appropriate mechanisms for their specific medical research requirements. Specialized tasks such as unimodal-related question answering, reading comprehension, reasoning, diagnosis, relation extraction, probability modeling, and others, as well as multimodal-related tasks like vision question answering, image captioning, cross-modal retrieval, report summarization, and generation, are discussed in detail. Each section delves into the intricate specifics of the respective method under consideration. This paper highlights the structures and advancements of medical domain explorations against general domain methods, emphasizing their applications across different tasks and datasets. It also outlines current challenges and opportunities for future medical domain research, paving the way for continued innovation and application in this rapidly evolving field. This comprehensive review serves not only as an academic resource but also delineates the course for future probes and utilization in the field of medical question answering.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 3","pages":"152-171"},"PeriodicalIF":0.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725294","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}
Hui Peng, Yashuo Zhang, Qun Luo, Xinyu Wang, Huijuan You
{"title":"Unfolding rates of 1:1 and 2:1 complex of CX-5461 and c-<i>MYC</i> promoter G-quadruplexes revealed by single-molecule force spectroscopy.","authors":"Hui Peng, Yashuo Zhang, Qun Luo, Xinyu Wang, Huijuan You","doi":"10.52601/bpr.2024.240018","DOIUrl":"10.52601/bpr.2024.240018","url":null,"abstract":"<p><p>CX-5461, also known as pidnarulex, is a strong G4 stabilizer and has received FDA fast-track designation for BRCA1- and BRCA2- mutated cancers. However, quantitative measurements of the unfolding rates of CX-5461-G4 complexes which are important for the regulation function of G4s, remain lacking. Here, we employ single-molecule magnetic tweezers to measure the unfolding force distributions of c-<i>MYC</i> G4s in the presence of different concentrations of CX-5461. The unfolding force distributions exhibit three discrete levels of unfolding force peaks, corresponding to three binding modes. In combination with a fluorescent quenching assay and molecular docking to previously reported ligand-c-<i>MYC</i> G4 structure, we assigned the ~69 pN peak corresponding to the 1:1 (ligand:G4) complex where CX-5461 binds at the G4's 5'-end. The ~84 pN peak is attributed to the 2:1 complex where CX-5461 occupies both the 5' and 3'. Furthermore, using the Bell-Arrhenius model to fit the unfolding force distributions, we determined the zero-force unfolding rates of 1:1, and 2:1 complexes to be (2.4 ± 0.9) × 10<sup>-8</sup> s<sup>-1</sup> and (1.4 ± 1.0) × 10<sup>-9</sup> s<sup>-1</sup> respectively. These findings provide valuable insights for the development of G4-targeted ligands to combat c-<i>MYC</i>-driven cancers.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 3","pages":"180-189"},"PeriodicalIF":0.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725298","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}
{"title":"Digital counting of force accumulation during mechanotransduction.","authors":"Xinyu Zhang, Bei Liu","doi":"10.52601/bpr.2024.240905","DOIUrl":"10.52601/bpr.2024.240905","url":null,"abstract":"","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 3","pages":"178-179"},"PeriodicalIF":0.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725295","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}
{"title":"Foundation models in molecular biology.","authors":"Yunda Si, Jiawei Zou, Yicheng Gao, Guohui Chuai, Qi Liu, Luonan Chen","doi":"10.52601/bpr.2024.240006","DOIUrl":"10.52601/bpr.2024.240006","url":null,"abstract":"<p><p>Determining correlations between molecules at various levels is an important topic in molecular biology. Large language models have demonstrated a remarkable ability to capture correlations from large amounts of data in the field of natural language processing as well as image generation, and correlations captured from data using large language models can also be applicable to solving a wide range of specific tasks, hence large language models are also referred to as foundation models. The massive amount of data that exists in the field of molecular biology provides an excellent basis for the development of foundation models, and the recent emergence of foundation models in the field of molecular biology has really pushed the entire field forward. We summarize the foundation models developed based on RNA sequence data, DNA sequence data, protein sequence data, single-cell transcriptome data, and spatial transcriptome data respectively, and further discuss the research directions for the development of foundation models in molecular biology.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 3","pages":"135-151"},"PeriodicalIF":0.0,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725296","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}
{"title":"Co-immunoprecipitation for identifying protein-protein interaction on lipid droplets.","authors":"Xiaochuan Fu, Shuyan Zhang, Pingsheng Liu","doi":"10.52601/bpr.2024.240007","DOIUrl":"10.52601/bpr.2024.240007","url":null,"abstract":"<p><p>The lipid droplet (LD) is a conserved organelle that exists in almost all organisms, ranging from bacteria to mammals. Dysfunctions in LDs are linked to a range of human metabolic syndromes. The formation of protein complexes on LDs is crucial for maintaining their function. Investigating how proteins interact on LDs is essential for understanding the role of LDs. We have developed an effective method to uncover protein-protein interactions and protein complexes specifically on LDs. In this method, we conduct co-immunoprecipitation (co-IP) experiments using LD proteins extracted directly from isolated LDs, rather than utilizing proteins from cell lysates. To elaborate, we begin by purifying LDs with high-quality and extracting LD-associated proteins. Subsequently, the co-IP experiment is performed on these LD-associated proteins directly, which would enhance the co-IP experiment specificity of LD-associated proteins. This method enables researchers to directly unveil protein complexes on LDs and gain deeper insights into the functional roles of proteins associated with LDs.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 2","pages":"102-110"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075374","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}
{"title":"Enrichment of ER tubule-derived microsomes by differential centrifugation and immunoprecipitation.","authors":"Yiduo Liu, Junjie Hu, Bing Yan","doi":"10.52601/bpr.2023.230031","DOIUrl":"10.52601/bpr.2023.230031","url":null,"abstract":"<p><p>The endoplasmic reticulum (ER) is an essential component of the endomembrane system in eukaryotes and plays a crucial role in protein and lipid synthesis, as well as the maintenance of calcium homeostasis. Morphologically, the ER is composed primarily of sheets and tubules. The tubular ER is composed of a network of tubular membrane structures, each with diameters ranging from 30 to 50 nanometers. In recent years, there has been in-depth research on the molecular mechanisms of membrane shaping and membrane fusion of the tubular ER. However, there is still limited understanding of the specific physiological functions of the tubular ER. Here, we report a protocol that combines differential centrifugation and immunoprecipitation to specifically enrich microsomes originating from the tubular ER in yeast. The ER tubule-derived microsomes can be further used for proteomic and lipidomic studies or other biochemical analyses.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 2","pages":"61-66"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075890","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}
{"title":"Exploring lysosomal biology: current approaches and methods.","authors":"Qiuyuan Yin, Chonglin Yang","doi":"10.52601/bpr.2023.230028","DOIUrl":"10.52601/bpr.2023.230028","url":null,"abstract":"<p><p>Lysosomes are the degradation centers and signaling hubs in the cell. Lysosomes undergo adaptation to maintain cell homeostasis in response to a wide variety of cues. Dysfunction of lysosomes leads to aging and severe diseases including lysosomal storage diseases (LSDs), neurodegenerative disorders, and cancer. To understand the complexity of lysosome biology, many research approaches and tools have been developed to investigate lysosomal functions and regulatory mechanisms in diverse experimental systems. This review summarizes the current approaches and tools adopted for studying lysosomes, and aims to provide a methodological overview of lysosomal research and related fields.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 2","pages":"111-120"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076476","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}
Miao Ye, Yuting Chen, Zhaojie Liu, Yigang Wang, Cong Yi
{"title":"Detection of ribophagy in yeast and mammals.","authors":"Miao Ye, Yuting Chen, Zhaojie Liu, Yigang Wang, Cong Yi","doi":"10.52601/bpr.2024.240002","DOIUrl":"10.52601/bpr.2024.240002","url":null,"abstract":"<p><p>Ribophagy, the cellular process wherein ribosomes are selectively self-digested through autophagy, plays a pivotal role in maintaining ribosome turnover. Understanding the molecular regulatory mechanisms governing ribophagy is pivotal to uncover its significance. Consequently, the establishment of methods for detecting ribophagy becomes important. In this protocol, we have optimized, enriched, and advanced existing ribophagy detection techniques, including immunoblotting, fluorescence microscopy, and transmission electron microscopy (TEM), to precisely monitor and quantify ribophagic events. Particularly noteworthy is the introduction of TEM technology for yeast ribophagy detection. In summary, the delineated methods are applicable for detecting ribophagy in both yeast and mammals, laying a solid foundation for further exploring the physiological importance of ribophagy and its potential implications in diverse cellular environments.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 2","pages":"82-101"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075696","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}
{"title":"Seeing is believing: observation of migrasomes.","authors":"Yuwei Huang, Li Yu","doi":"10.52601/bpr.2023.230024","DOIUrl":"10.52601/bpr.2023.230024","url":null,"abstract":"<p><p>Migrasomes are a novel type of cell organelle that form on the retraction fibers at the rear of migrating cells. In recent years, numerous studies have unveiled the mechanisms of migrasome formation and have highlighted significant roles of migrasomes in both physiological and pathological processes. Building upon the strategies outlined in published works and our own research experiences, we have compiled a comprehensive set of protocols for observing migrasomes. These step-by-step instructions encompass various aspects such as cell culture, labeling, imaging, <i>in vitro</i> reconstitution, and statistical analysis. We believe that these protocols serve as a valuable resource for researchers exploring migrasome biology.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 2","pages":"67-81"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11103717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076908","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}