FedBrain: Federated Training of Graph Neural Networks for Connectome-based Brain Imaging Analysis
Pac Symp Biocomput. 2024;29:214-225.ABSTRACTRecent advancements in neuroimaging techniques have sparked a growing interest in understanding the complex interactions between anatomical regions of interest (ROIs), forming into brain networks that play a crucial role in various clinical tasks, such as neural pattern discovery and disorder diagnosis. In recent years, graph neural networks (GNNs) have emerged as powerful tools for analyzing network data. However, due to the complexity of data acquisition and regulatory restrictions, brain network studies remain limited in scale and are often confined to local institutions. Thes...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Yi Yang Han Xie Hejie Cui Carl Yang Source Type: research
Session Introduction: Drug-repurposing and discovery in the era of "big" real-world data: how the incorporation of observational data, genetics, and other -omic technologies can move us forward
Pac Symp Biocomput. 2024;29:226-231.ABSTRACTThis PSB 2024 session discusses the many broad biological, computational, and statistical approaches currently being used for therapeutic drug target identification and repurposing of existing treatments. Drug repurposing efforts have the potential to dramatically improve the treatment landscape by more rapidly identifying drug targets and alternative strategies for untreated or poorly managed diseases. The overarching theme for this session is the use and integration of real-world data to identify drug-disease pairs with potential therapeutic use. These drug-disease pairs may be...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Megan M Shuey Jacklyn N Hellwege Nikhil Khankari Marijana Vujkovic Todd L Edwards Source Type: research
Systematic Estimation of Treatment Effect on Hospitalization Risk as a Drug Repurposing Screening Method
Pac Symp Biocomput. 2024;29:232-246.ABSTRACTDrug repurposing (DR) intends to identify new uses for approved medications outside their original indication. Computational methods for finding DR candidates usually rely on prior biological and chemical information on a specific drug or target but rarely utilize real-world observations. In this work, we propose a simple and effective systematic screening approach to measure medication impact on hospitalization risk based on large-scale observational data. We use common classification systems to group drugs and diseases into broader functional categories and test for non-zero ef...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Costa Georgantas Jaume Banus Roger Hullin Jonas Richiardi Source Type: research
Transcript-aware analysis of rare predicted loss-of-function variants in the UK Biobank elucidate new isoform-trait associations
Pac Symp Biocomput. 2024;29:247-260.ABSTRACTA single gene can produce multiple transcripts with distinct molecular functions. Rare-variant association tests often aggregate all coding variants across individual genes, without accounting for the variants' presence or consequence in resulting transcript isoforms. To evaluate the utility of transcript-aware variant sets, rare predicted loss-of-function (pLOF) variants were aggregated for 17,035 protein-coding genes using 55,558 distinct transcript-specific variant sets. These sets were tested for their association with 728 circulating proteins and 188 quantitative phenotypes ...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Rachel A Hoffing Aimee M Deaton Aaron M Holleman Lynne Krohn Philip J LoGerfo Mollie E Plekan Sebastian Akle Serrano Paul Nioi Lucas D Ward Source Type: research
Generating new drug repurposing hypotheses using disease-specific hypergraphs
Pac Symp Biocomput. 2024;29:261-275.ABSTRACTThe drug development pipeline for a new compound can last 10-20 years and cost over $10 billion. Drug repurposing offers a more time- and cost-effective alternative. Computational approaches based on network graph representations, comprising a mixture of disease nodes and their interactions, have recently yielded new drug repurposing hypotheses, including suitable candidates for COVID-19. However, these interactomes remain aggregate by design and often lack disease specificity. This dilution of information may affect the relevance of drug node embeddings to a particular disease, ...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Ayush Jain Marie-Laure Charpignon Irene Y Chen Anthony Philippakis Ahmed Alaa Source Type: research
Combined kinome inhibition states are predictive of cancer cell line sensitivity to kinase inhibitor combination therapies
Pac Symp Biocomput. 2024;29:276-290.ABSTRACTProtein kinases are a primary focus in targeted therapy development for cancer, owing to their role as regulators in nearly all areas of cell life. Recent strategies targeting the kinome with combination therapies have shown promise, such as trametinib and dabrafenib in advanced melanoma, but empirical design for less characterized pathways remains a challenge. Computational combination screening is an attractive alternative, allowing in-silico filtering prior to experimental testing of drastically fewer leads, increasing efficiency and effectiveness of drug development pipelines...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Chinmaya U Joisa Kevin A Chen Samantha Beville Timothy Stuhlmiller Matthew E Berginski Denis Okumu Brian T Golitz Michael P East Gary L Johnson Shawn M Gomez Source Type: research
Creation of a Curated Database of Experimentally Determined Human Protein Structures for the Identification of Its Targetome
Pac Symp Biocomput. 2024;29:291-305.ABSTRACTAssembling an "integrated structural map of the human cell" at atomic resolution will require a complete set of all human protein structures available for interaction with other biomolecules - the human protein structure targetome - and a pipeline of automated tools that allow quantitative analysis of millions of protein-ligand interactions. Toward this goal, we here describe the creation of a curated database of experimentally determined human protein structures. Starting with the sequences of 20,422 human proteins, we selected the most representative structure for each protein ...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Armand Ovanessians Carson Snow Thomas Jennewein Susanta Sarkar Gil Speyer Judith Klein-Seetharaman Source Type: research
Modeling Path Importance for Effective Alzheimer's Disease Drug Repurposing
Pac Symp Biocomput. 2024;29:306-321.ABSTRACTRecently, drug repurposing has emerged as an effective and resource-efficient paradigm for AD drug discovery. Among various methods for drug repurposing, network-based methods have shown promising results as they are capable of leveraging complex networks that integrate multiple interaction types, such as protein-protein interactions, to more effectively identify candidate drugs. However, existing approaches typically assume paths of the same length in the network have equal importance in identifying the therapeutic effect of drugs. Other domains have found that same length paths...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Shunian Xiang Patrick J Lawrence Bo Peng ChienWei Chiang Dokyoon Kim Li Shen Xia Ning Source Type: research
Session Introduction: Overcoming health disparities in precision medicine
ConclusionAcknowledgments.PMID:38160289 (Source: Pacific Symposium on Biocomputing)
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Francisco M De La Vega Kathleen C Barnes Keolu Fox Alexander Ioannidis Eimear Kenny Rasika A Mathias Bogdan Pasaniuc Source Type: research
PopGenAdapt: Semi-Supervised Domain Adaptation for Genotype-to-Phenotype Prediction in Underrepresented Populations
Pac Symp Biocomput. 2024;29:327-340.ABSTRACTThe lack of diversity in genomic datasets, currently skewed towards individuals of European ancestry, presents a challenge in developing inclusive biomedical models. The scarcity of such data is particularly evident in labeled datasets that include genomic data linked to electronic health records. To address this gap, this paper presents PopGenAdapt, a genotype-to-phenotype prediction model which adopts semi-supervised domain adaptation (SSDA) techniques originally proposed for computer vision. PopGenAdapt is designed to leverage the substantial labeled data available from indivi...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Mar çal Comajoan Cara Daniel Mas Montserrat Alexander G Ioannidis Source Type: research
LA-GEM: imputation of gene expression with incorporation of Local Ancestry
Pac Symp Biocomput. 2024;29:341-358.ABSTRACTGene imputation and TWAS have become a staple in the genomics medicine discovery space; helping to identify genes whose regulation effects may contribute to disease susceptibility. However, the cohorts on which these methods are built are overwhelmingly of European Ancestry. This means that the unique regulatory variation that exist in non-European populations, specifically African Ancestry populations, may not be included in the current models. Moreover, African Americans are an admixed population, with a mix of European and African segments within their genome. No gene imputati...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Mrinal Mishra Layan Nahlawi Yizhen Zhong Tanima De Guang Yang Cristina Alarcon Minoli A Perera Source Type: research
Cluster Analysis reveals Socioeconomic Disparities among Elective Spine Surgery Patients
Pac Symp Biocomput. 2024;29:359-373.ABSTRACTThis work demonstrates the use of cluster analysis in detecting fair and unbiased novel discoveries. Given a sample population of elective spinal fusion patients, we identify two overarching subgroups driven by insurance type. The Medicare group, associated with lower socioeconomic status, exhibited an over-representation of negative risk factors. The findings provide a compelling depiction of the interwoven socioeconomic and racial disparities present within the healthcare system, highlighting their consequential effects on health inequalities. The results are intended to guide ...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Alena Orlenko Philip J Freda Attri Ghosh Hyunjun Choi Nicholas Matsumoto Tiffani J Bright Corey T Walker Tayo Obafemi-Ajayi Jason H Moore Source Type: research
Evidence of recent and ongoing admixture in the U.S. and influences on health and disparities
Pac Symp Biocomput. 2024;29:374-388.ABSTRACTMany researchers in genetics and social science incorporate information about race in their work. However, migrations (historical and forced) and social mobility have brought formerly separated populations of humans together, creating younger generations of individuals who have more complex and diverse ancestry and race profiles than older age groups. Here, we sought to better understand how temporal changes in genetic admixture influence levels of heterozygosity and impact health outcomes. We evaluated variation in genetic ancestry over 100 birth years in a cohort of 35,842 indi...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Hannah M Seagle Jacklyn N Hellwege Brian S Mautz Chun Li Yaomin Xu Siwei Zhang Dan M Roden Tracy L McGregor Digna R Velez Edwards Todd L Edwards Source Type: research
Evaluating the relationships between genetic ancestry and the clinical phenome
In this study, we leverage the biobank from Vanderbilt University Medical Center, BioVU, to investigate relationships between genetic ancestry proportion and the clinical phenome. For all samples in BioVU, we calculated six ancestry proportions based on 1000 Genomes references: eastern African (EAFR), western African (WAFR), northern European (NEUR), southern European (SEUR), eastern Asian (EAS), and southern Asian (SAS). From PheWAS, we found phecode categories significantly enriched neoplasms for EAFR, WAFR, and SEUR, and pregnancy complication in SEUR, NEUR, SAS, and EAS (p < 0.003). We then selected phenotypes hyper...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: Jacqueline A Piekos Jeewoo Kim Jacob M Keaton Jacklyn N Hellwege Todd L Edwards Digna R Velez Edwards Source Type: research
Machine Learning Strategies for Improved Phenotype Prediction in Underrepresented Populations
This study introduces an adaptable machine learning toolkit that integrates multiple existing methodologies and novel techniques to enhance the prediction accuracy for underrepresented populations in genomic datasets. By leveraging machine learning techniques, including gradient boosting and automated methods, coupled with novel population-conditional re-sampling techniques, our method significantly improves the phenotypic prediction from single nucleotide polymorphism (SNP) data for diverse populations. We evaluate our approach using the UK Biobank, which is composed primarily of British individuals with European ancestry...
Source: Pacific Symposium on Biocomputing - December 31, 2023 Category: Bioinformatics Authors: David Bonet May Levin Daniel Mas Montserrat Alexander G Ioannidis Source Type: research
