Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing最新文献

{"title":"Improving Retrieval-Augmented Generation in Medicine with Iterative Follow-up Questions.","authors":"Guangzhi Xiong, Qiao Jin, Xiao Wang, Minjia Zhang, Zhiyong Lu, Aidong Zhang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The emergent abilities of large language models (LLMs) have demonstrated great potential in solving medical questions. They can possess considerable medical knowledge, but may still hallucinate and are inflexible in the knowledge updates. While Retrieval-Augmented Generation (RAG) has been proposed to enhance the medical question-answering capabilities of LLMs with external knowledge bases, it may still fail in complex cases where multiple rounds of information-seeking are required. To address such an issue, we propose iterative RAG for medicine (i-MedRAG), where LLMs can iteratively ask follow-up queries based on previous information-seeking attempts. In each iteration of i-MedRAG, the follow-up queries will be answered by a vanilla RAG system and they will be further used to guide the query generation in the next iteration. Our experiments show the improved performance of various LLMs brought by i-MedRAG compared with vanilla RAG on complex questions from clinical vignettes in the United States Medical Licensing Examination (USMLE), as well as various knowledge tests in the Massive Multitask Language Understanding (MMLU) dataset. Notably, our zero-shot i-MedRAG outperforms all existing prompt engineering and fine-tuning methods on GPT-3.5, achieving an accuracy of 69.68% on the MedQA dataset. In addition, we characterize the scaling properties of i-MedRAG with different iterations of follow-up queries and different numbers of queries per iteration. Our case studies show that i-MedRAG can flexibly ask follow-up queries to form reasoning chains, providing an in-depth analysis of medical questions. To the best of our knowledge, this is the first-of-its-kind study on incorporating follow-up queries into medical RAG.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"199-214"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency of adding salt is a stronger predictor of chronic kidney disease in individuals with genetic risk.","authors":"Manu Shivakumar, Yanggyun Kim, Sang-Hyuk Jung, Jakob Woerner, Dokyoon Kim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The incidence of chronic kidney disease (CKD) is increasing worldwide, but there is no specific treatment available. Therefore, understanding and controlling the risk factors for CKD are essential for preventing disease occurrence. Salt intake raises blood pressure by increasing fluid volume and contributes to the deterioration of kidney function by enhancing the renin-angiotensin system and sympathetic tone. Thus, a low-salt diet is important to reduce blood pressure and prevent kidney diseases. With recent advancements in genetic research, our understanding of the etiology and genetic background of CKD has deepened, enabling the identification of populations with a high genetic predisposition to CKD. It is thought that the impact of lifestyle or environmental factors on disease occurrence or prevention may vary based on genetic factors. This study aims to investigate whether frequency of adding salt has different effects depending on genetic risk for CKD. CKD polygenic risk scores (PRS) were generated using CKDGen Consortium GWAS (N= 765,348) summary statics. Then we applied the CKD PRS to UK Biobank subjects. A total of 331,318 European individuals aged 40-69 without CKD were enrolled in the study between 2006-2010. The average age at enrollment of the participants in this study was 56.69, and 46% were male. Over an average follow-up period of 8 years, 12,279 CKD cases were identified. The group that developed CKD had a higher percentage of individuals who added salt (46.37% vs. 43.04%) and higher CKD high-risk PRS values compared to the group that did not develop CKD (23.53% vs. 19.86%). We classified the individuals into four groups based on PRS: low (0-19%), intermediate (20-79%), high (80-94%), very high (≥ 95%). Incidence of CKD increased incrementally according to CKD PRS even after adjusting for age, sex, race, Townsend deprivation index, body mass index, estimated glomerular filtration rate, smoking, alcohol, physical activity, diabetes mellitus, dyslipidemia, hypertension, coronary artery diseases, cerebrovascular diseases at baseline. Compared to the \"never/rarely\" frequency of adding salt group, \"always\" frequency of adding salt group had an increasing incidence of CKD proportionate to the degree of frequency of adding salt. However, the significant association of \"always\" group on incident CKD disappeared in the low PRS group. This study validated the signal from PRSs for CKD across a large cohort and confirmed that frequency of adding salt contributes to the occurrence of CKD. Additionally, it confirmed that the effect of frequency of \"always\" adding salt on CKD incidence is greater in those with more than intermediate CKD-PRS. This study suggests that increased salt intake is particularly concerning for individuals with genetic risk factors for CKD, underscoring the clinical importance of reducing salt intake for these individuals.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"551-564"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Dynamic Model for Early Prediction of Alzheimer's Disease by Leveraging Graph Convolutional Networks and Tensor Algebra.","authors":"Cagri Ozdemir, Mohammad Al Olaimat, Serdar Bozdag","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurocognitive disorder that deteriorates memory and impairs cognitive functions. Mild Cognitive Impairment (MCI) is generally considered as an intermediate phase between normal cognitive aging and more severe conditions such as AD. Although not all individuals with MCI will develop AD, they are at an increased risk of developing AD. Diagnosing AD once strong symptoms are already present is of limited value, as AD leads to irreversible cognitive decline and brain damage. Thus, it is crucial to develop methods for the early prediction of AD in individuals with MCI. Recurrent Neural Networks (RNN)-based methods have been effectively used to predict the progression from MCI to AD by analyzing electronic health records (EHR). However, despite their widespread use, existing RNN-based tools may introduce increased model complexity and often face difficulties in capturing long-term dependencies. In this study, we introduced a novel Dynamic deep learning model for Early Prediction of AD (DyEPAD) to predict MCI subjects' progression to AD utilizing EHR data. In the first phase of DyEPAD, embeddings for each time step or visit are captured through Graph Convolutional Networks (GCN) and aggregation functions. In the final phase, DyEPAD employs tensor algebraic operations for frequency domain analysis of these embeddings, capturing the full scope of evolutionary patterns across all time steps. Our experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Alzheimer's Coordinating Center (NACC) datasets demonstrate that our proposed model outperforms or is in par with the state-of-the-art and baseline methods.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"675-689"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819308","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":"The Impact of Ancestry on Genome-Wide Association Studies.","authors":"Steven Christopher Jones, Katie M Cardone, Yuki Bradford, Sarah A Tishkoff, Marylyn D Ritchie","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Genome-wide association studies (GWAS) are an important tool for the study of complex disease genetics. Decisions regarding the quality control (QC) procedures employed as part of a GWAS can have important implications on the results and their biological interpretation. Many GWAS have been conducted predominantly in cohorts of European ancestry, but many initiatives aim to increase the representation of diverse ancestries in genetic studies. The question of how these data should be combined and the consequences that genetic variation across ancestry groups might have on GWAS results warrants further investigation. In this study, we focus on several commonly used methods for combining genetic data across diverse ancestry groups and the impact these decisions have on the outcome of GWAS summary statistics. We ran GWAS on two binary phenotypes using ancestry-specific, multi-ancestry mega-analysis, and meta-analysis approaches. We found that while multi-ancestry mega-analysis and meta-analysis approaches can aid in identifying signals shared across ancestries, they can diminish the signal of ancestry-specific associations and modify their effect sizes. These results demonstrate the potential impact on downstream post-GWAS analyses and follow-up studies. Decisions regarding how the genetic data are combined has the potential to mask important findings that might serve individuals of ancestries that have been historically underrepresented in genetic studies. New methods that consider ancestry-specific variants in conjunction with the shared variants need to be developed.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"251-267"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819315","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":"Uncovering Important Diagnostic Features for Alzheimer's, Parkinson's and Other Dementias Using Interpretable Association Mining Methods.","authors":"Kazi Noshin, Mary Regina Boland, Bojian Hou, Victoria Lu, Carol Manning, Li Shen, Aidong Zhang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Alzheimer's Disease and Related Dementias (ADRD) afflict almost 7 million people in the USA alone. The majority of research in ADRD is conducted using post-mortem samples of brain tissue or carefully recruited clinical trial patients. While these resources are excellent, they suffer from lack of sex/gender, and racial/ethnic inclusiveness. Electronic Health Records (EHR) data has the potential to bridge this gap by including real-world ADRD patients treated during routine clinical care. In this study, we utilize EHR data from a cohort of 70,420 ADRD patients diagnosed and treated at Penn Medicine. Our goal is to uncover important risk features leading to three types of Neuro-Degenerative Disorders (NDD), including Alzheimer's Disease (AD), Parkinson's Disease (PD) and Other Dementias (OD). We employ a variety of Machine Learning (ML) Methods, including uni-variate and multivariate ML approaches and compare accuracies across the ML methods. We also investigate the types of features identified by each method, the overlapping features and the unique features to highlight important advantages and disadvantages of each approach specific for certain NDD types. Our study is important for those interested in studying ADRD and NDD in EHRs as it highlights the strengths and limitations of popular approaches employed in the ML community. We found that the uni-variate approach was able to uncover features that were important and rare for specific types of NDD (AD, PD, OD), which is important from a clinical perspective. Features that were found across all methods represent features that are the most robust.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"631-646"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819326","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":"Command line to pipeLine: Cross-biobank analyses with Nextflow.","authors":"Anurag Verma, Zachary Rodriguez, Lindsay Guare, Katie Cardone, Christopher Carson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Biobanks hold immense potential for genomic research, but fragmented data and incompatible tools slow progress. This workshop equipped participants with Nextflow, a powerful workflow language to streamline bioinformatic analyses across biobanks. We taught participants to write code in their preferred language and demonstrated how Nextflow handles the complexities, ensuring consistent, reproducible results across different platforms. This interactive session was ideal for beginner-to-intermediate researchers who want to (1) Leverage biobank data for genomic discoveries, (2) Build portable and scalable analysis pipelines, (3) Ensure reproducibility in their findings, (4) Gain hands-on experience through presentations, demonstrations, tutorials, and discussions with bioinformatics experts.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"696-701"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electronic Health Record Analysis for Personalized Medicine: Predicting Malnutrition-Related Health Outcomes and Secondary Neuropsychiatric Health Concerns.","authors":"Pinar Gurkas, Gunnur Karakurt","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Malnutrition poses risks regarding cognitive, behavioral, and physical well-being. The aim of this study was to investigate the prevalent health issues associated with malnutrition by utilizing electronic health records (EHR) data. The IBM Watson Health, Explorys platform was used to access the EHR data. Two cohorts were created by two queries; patients with a history of malnutrition (n=5180) and patients without a history of malnutrition diagnosis (n= 413890). The log odds ratio and χ2 statistic were used to identify the statistically significant differences between these two cohorts. We found that there were 35 terms that were more common among the cohort with the malnutrition diagnosis. These terms were categorized under developmental anomalies, infectious agents, respiratory system issues, digestive system issues, pregnancy/prenatal problems, mental, behavioral, or neurodevelopmental disorders, diseases of the ear or mastoid process, diseases of the visual system, and chromosomal anomalies. The management of malnutrition in children is a complex problem that can be addressed with a multifactorial approach. Based on the key themes emerging from among the commonly prevalent terms identified in our study, infection prevention, education in appropriate nutritional solutions for digestive health issues, supportive services to address neurodevelopmental needs, and quality prenatal healthcare would constitute beneficial prevention efforts. Improving our understanding of malnutrition is necessary to develop new interventions for prevention and treatment.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"599-613"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819518","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":"A Comprehensive Bibliometric Analysis: Celebrating the Thirtieth Anniversary of the Pacific Symposium on Biocomputing.","authors":"Rachit Kumar, Rasika Venkatesh, David Y Zhang, Teri E Klein, Marylyn D Ritchie","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The 2025 Pacific Symposium on Biocomputing (PSB) represents a remarkable milestone, as it is the thirtieth anniversary of PSB. We use this opportunity to analyze the bibliometric output of 30 years of PSB publications in a wide range of analyses with a focus on various eras that represent important disruptive breakpoints in the field of bioinformatics and biocomputing. These include an analysis of paper topics and keywords, flight emissions produced by travel to PSB by authors, citation and co-authorship networks and metrics, and a broad assessment of diversity and representation in PSB authors. We use the results of these analyses to identify insights that we can carry forward to the upcoming decades of PSB.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819304","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":"Connecting intermediate phenotypes to disease using multi-omics in heart failure.","authors":"Anni Moore, Rasika Venkatesh, Michael G Levin, Scott M Damrauer, Nosheen Reza, Thomas P Cappola, Marylyn D Ritchie","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Heart failure (HF) is one of the most common, complex, heterogeneous diseases in the world, with over 1-3% of the global population living with the condition. Progression of HF can be tracked via MRI measures of structural and functional changes to the heart, namely left ventricle (LV), including ejection fraction, mass, end-diastolic volume, and LV end-systolic volume. Moreover, while genome-wide association studies (GWAS) have been a useful tool to identify candidate variants involved in HF risk, they lack crucial tissue-specific and mechanistic information which can be gained from incorporating additional data modalities. This study addresses this gap by incorporating transcriptome-wide and proteome-wide association studies (TWAS and PWAS) to gain insights into genetically-regulated changes in gene expression and protein abundance in precursors to HF measured using MRI-derived cardiac measures as well as full-stage all-cause HF. We identified several gene and protein overlaps between LV ejection fraction and end-systolic volume measures. Many of the overlaps identified in MRI-derived measurements through TWAS and PWAS appear to be shared with all-cause HF. We implicate many putative pathways relevant in HF associated with these genes and proteins via gene-set enrichment and protein-protein interaction network approaches. The results of this study (1) highlight the benefit of using multi-omics to better understand genetics and (2) provide novel insights as to how changes in heart structure and function may relate to HF.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"504-521"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819496","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":"Session Introduction: Translating Big Data Imaging Genomics Findings to the Individual: Prediction of Risks and Outcomes in Neuropsychiatric Illnesses.","authors":"Peter Kochunov, Li Shen, Zhongming Zhao, Paul M Thompson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This PSB 2025 session is focused on opportunities, challenges and solutions for translating Big Data Imaging Genomic findings toward powering decision making in personalized medicine and guiding individual clinical decisions. It combines many of the scientific directions that are of interest to PSB members including Big Data analyses, pattern recognition, machine learning and AI, electronic health records and others.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"594-598"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}