Sutanu Nandi, Yuehua Zhu, Lucas A Gillenwater, Marc Subirana-Granés, Haoyu Zhang, Negar Janani, Casey Greene, Milton Pividori, Maria Chikina, James C Costello
{"title":"A Pathway-Level Information ExtractoR (PLIER) framework to gain mechanistic insights into obesity in Down syndrome.","authors":"Sutanu Nandi, Yuehua Zhu, Lucas A Gillenwater, Marc Subirana-Granés, Haoyu Zhang, Negar Janani, Casey Greene, Milton Pividori, Maria Chikina, James C Costello","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Down syndrome (DS), caused by the triplication of chromosome 21 (T21), is a prevalent genetic disorder with a higher incidence of obesity. Traditional approaches have struggled to differentiate T21-specific molecular dysregulation from general obesity-related processes. This study introduces the omni-PLIER framework, combining the Pathway-Level Information ExtractoR (PLIER) with the omnigenic model, to uncover molecular mechanisms underlying obesity in DS. The PLIER framework aligns gene expression data with biological pathways, facilitating the identification of relevant molecular patterns. Using RNA sequencing data from the Human Trisome Project, omni-PLIER identified latent variables (LVs) significantly associated with both T21 and body mass index (BMI). Elastic net regression and causal mediation analysis revealed LVs mediating the effect of karyotype on BMI. Notably, LVs involving glutathione peroxidase-1 (GPX1) and MCL1 apoptosis regulator, BCL2 family members emerged as crucial mediators. These findings provide insights into the molecular interplay between DS and obesity. The omni-PLIER model offers a robust methodological advancement for dissecting complex genetic disorders, with implications for understanding obesity-related processes in both DS and the general population.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"412-425"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819311","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}
Olivia Wen, Samuel C Wolff, Wayne Stallaert, Didong Li, Jeremy E Purvis, Tarek M Zikry
{"title":"Spherical Manifolds Capture Drug-Induced Changes in Tumor Cell Cycle Behavior.","authors":"Olivia Wen, Samuel C Wolff, Wayne Stallaert, Didong Li, Jeremy E Purvis, Tarek M Zikry","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>CDK4/6 inhibitors such as palbociclib block cell cycle progression and improve outcomes for many ER+/HER2- breast cancer patients. Unfortunately, many patients are initially resistant to the drug or develop resistance over time in part due to heterogeneity among individual tumor cells. To better understand these mechanisms of resistance, we used multiplex, single-cell imaging to profile cell cycle proteins in ER+ breast tumor cells under increasing palbociclib concentrations. We then applied spherical principal component analysis (SPCA), a dimensionality reduction method that leverages the inherently cyclical nature of the high-dimensional imaging data, to look for changes in cell cycle behavior in resistant cells. SPCA characterizes data as a hypersphere and provides a framework for visualizing and quantifying differences in cell cycles across treatment-induced perturbations. The hypersphere representations revealed shifts in the mean cell state and population heterogeneity. SPCA validated expected trends of CDK4/6 inhibitor response such as decreased expression of proliferation markers (Ki67, pRB), but also revealed potential mechanisms of resistance including increased expression of cyclin D1 and CDK2. Understanding the molecular mechanisms that allow treated tumor cells to evade arrest is critical for identifying targets of future therapies. Ultimately, we seek to further SPCA as a tool of precision medicine, targeting treatments by individual tumors, and extending this computational framework to interpret other cyclical biological processes represented by high-dimensional data.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"473-487"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819378","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}
Jared M Phillips, Julie A Schneider, David A Bennett, Paul K Crane, Shannon L Risacher, Andrew J Saykin, Logan C Dumitrescu, Timothy J Hohman
{"title":"Astrocyte Reactivity Polygenic Risk Score May Predict Cognitive Decline in Alzheimer's Disease.","authors":"Jared M Phillips, Julie A Schneider, David A Bennett, Paul K Crane, Shannon L Risacher, Andrew J Saykin, Logan C Dumitrescu, Timothy J Hohman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a polygenic disorder with a prolonged prodromal phase, complicating early diagnosis. Recent research indicates that increased astrocyte reactivity is associated with a higher risk of pathogenic tau accumulation, particularly in amyloid-positive individuals. However, few clinical tools are available to predict which individuals are likely to exhibit elevated astrocyte activation and, consequently, be susceptible to hyperphosphorylated tau-induced neurodegeneration. Polygenic risk scores (PRS) aggregate the effects of multiple genetic loci to provide a single, continuous metric representing an individual's genetic risk for a specific phenotype. We hypothesized that an astrocyte activation PRS could aid in the early detection of faster clinical decline. Therefore, we constructed an astrocyte activation PRS and assessed its predictive value for cognitive decline and AD biomarkers (i.e., cerebrospinal fluid [CSF] levels of Aβ1-42, total tau, and p-tau181) in a cohort of 791 elderly individuals. The astrocyte activation PRS showed significant main effects on cross-sectional memory (β = -0.07, p = 0.03) and longitudinal executive function (β = -0.01, p = 0.03). Additionally, the PRS interacted with amyloid positivity (p.intx = 0.02), whereby indicating that amyloid burden modifies the association between the PRS and annual rate of language decline. Furthermore, the PRS was negatively associated with CSF Aβ1-42 levels (β = -3.4, p = 0.07) and interacted with amyloid status, such that amyloid burden modifies the association between the PRS and CSF phosphorylated tau levels (p.intx = 0.08). These findings suggest that an astrocyte activation PRS could be a valuable tool for early disease risk prediction, potentially enabling intervention during the interval between pathogenic amyloid and tau accumulation.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"488-503"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819425","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}
Lindsay A Guare, Jagyashila Das, Lannawill Caruth, Shefali Setia-Verma
{"title":"Social Determinants of Health and Lifestyle Risk Factors Modulate Genetic Susceptibility for Women's Health Outcomes.","authors":"Lindsay A Guare, Jagyashila Das, Lannawill Caruth, Shefali Setia-Verma","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Women's health conditions are influenced by both genetic and environmental factors. Understanding these factors individually and their interactions is crucial for implementing preventative, personalized medicine. However, since genetics and environmental exposures, particularly social determinants of health (SDoH), are correlated with race and ancestry, risk models without careful consideration of these measures can exacerbate health disparities. We focused on seven women's health disorders in the All of Us Research Program: breast cancer, cervical cancer, endometriosis, ovarian cancer, preeclampsia, uterine cancer, and uterine fibroids. We computed polygenic risk scores (PRSs) from publicly available weights and tested the effect of the PRSs on their respective phenotypes as well as any effects of genetic risk on age at diagnosis. We next tested the effects of environmental risk factors (BMI, lifestyle measures, and SDoH) on age at diagnosis. Finally, we examined the impact of environmental exposures in modulating genetic risk by stratified logistic regressions for different tertiles of the environment variables, comparing the effect size of the PRS. Of the twelve sets of weights for the seven conditions, nine were significantly and positively associated with their respective phenotypes. None of the PRSs was associated with different ages at diagnoses in the time-to-event analyses. The highest environmental risk group tended to be diagnosed earlier than the low and medium-risk groups. For example, the cases of breast cancer, ovarian cancer, uterine cancer, and uterine fibroids in highest BMI tertile were diagnosed significantly earlier than the low and medium BMI groups, respectively). PRS regression coefficients were often the largest in the highest environment risk groups, showing increased susceptibility to genetic risk. This study's strengths include the diversity of the All of Us study cohort, the consideration of SDoH themes, and the examination of key risk factors and their interrelationships. These elements collectively underscore the importance of integrating genetic and environmental data to develop more precise risk models, enhance personalized medicine, and ultimately reduce health disparities.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"296-313"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819270","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}
Alexis T Akerele, Jacqueline A Piekos, Jeewoo Kim, Nikhil K Khankari, Jacklyn N Hellwege, Todd L Edwards, Digna R Velez Edwards
{"title":"Uterine fibroids show evidence of shared genetic architecture with blood pressure traits.","authors":"Alexis T Akerele, Jacqueline A Piekos, Jeewoo Kim, Nikhil K Khankari, Jacklyn N Hellwege, Todd L Edwards, Digna R Velez Edwards","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Uterine leiomyomata (fibroids, UFs) are common, benign tumors in females, having an estimated prevalence of up to 80%. They are fibrous masses growing within the myometrium leading to chronic symptoms like dysmenorrhea, abnormal uterine bleeding, anemia, severe pelvic pain, and infertility. Hypertension (HTN) is a common risk factor for UFs, though less prevalent in premenopausal individuals. While observational studies have indicated strong associations between UFs and HTN, the biological mechanisms linking the two conditions remain unclear. Understanding the relationship between HTN and UFs is crucial because UFs and HTN lead to substantial comorbidities adversely impacting female health. Identifying the common underlying biological mechanisms can improve treatment strategies for both conditions. To clarify the genetic and causal relationships between UFs and BP, we conducted a bidirectional, two-sample Mendelian randomization (MR) analysis and evaluated the genetic correlations across BP traits and UFs. We used data from a multi-ancestry genome-wide association study (GWAS) meta-analysis of UFs (44,205 cases and 356,552 controls), and data from a cross-ancestry GWAS meta-analysis of BP phenotypes (diastolic BP [DBP], systolic BP [SBP], and pulse pressure [PP], N=447,758). We evaluated genetic correlation of BP phenotypes and UFs with linkage disequilibrium score regression (LDSC). LDSC results indicated a positive genetic correlation between DBP and UFs (Rg=0.132, p<5.0x10-5), and SBP and UFs (Rg=0.063, p<2.5x10-2). MR using UFs as the exposure and BP traits as outcomes indicated a relationship where UFs increases DBP (odds ratio [OR]=1.20, p<2.7x10-3). Having BP traits as exposures and UFs as the outcome showed that DBP and SBP increase risk for UFs (OR =1.04, p<2.2x10-3; OR=1.00, p<4.0x10-2; respectively). Our results provide evidence of shared genetic architecture and pleiotropy between HTN and UFs, suggesting common biological pathways driving their etiologies. Based on these findings, DBP appears to be a stronger risk factor for UFs compared to SBP and PP.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"281-295"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819424","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}
Yewen Huang, Syed Ibrar Hussain, Demetrio Labate, Robert Azencott, Paul Thompson, Bhim Adhikari, Peter Kochunov
{"title":"Exploring the Granularity of the Illnesses-Related Changes in Regional Homogeneity in Major Depressive Disorder using the UKBB Data.","authors":"Yewen Huang, Syed Ibrar Hussain, Demetrio Labate, Robert Azencott, Paul Thompson, Bhim Adhikari, Peter Kochunov","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Illness related brain effects of neuropsychiatric disorders are not regionally uniform, with some regions showing large pathological effects while others are relatively spared. Presently, Big Data meta-analytic studies tabulate these effects using structural and/or functional brain atlases that are based on the anatomical boundaries, landmarks and connectivity patterns in healthy brains. These patterns are then translated to individual level predictors using approaches such as Regional Vulnerability Index (RVI), which quantifies the agreement between individual brain patterns and the canonical pattern found in the illness. However, the atlases from healthy brains are unlikely to align with deficit pattern expressed in specific disorders such as Major Depressive Disorder (MDD), thus reducing the statistical power for individualized predictions. Here, we evaluated a novel approach, where disorder specific templates are constructed using the Kullback-Leibler (KL) distance to balance granularity, signal-to-noise ratio and the contrast between regional effect sizes to maximize translatability of the population-wide illness pattern at the level of the individual. We used regional homogeneity (ReHo) maps extracted from resting state functional MRI for N = 2, 289 MDD sample (mean age ± s.d.: 63.2 ± 7.2 years) and N = 6104 control subjects (mean age ± s.d.: 62.9 ± 7.2 years) who were free of MDD and any other mental condition. The cortical effects of MDD were analyzed on the 3D spherical surfaces representing cerebral hemispheres. KL-distance was used to organize the cortical surface into 28 regions of interest based on effect sizes, connectivity and signal-to-noise ratio. The RVI values calculated using this novel approach showed significantly higher effect size of the illness than these calculated using standard Desikan brain atlas.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"30 ","pages":"647-663"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819527","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}
Gokul Srinivasan, Matthew J Davis, Matthew R LeBoeuf, Michael Fatemi, Zarif L Azher, Yunrui Lu, Alos B Diallo, Marietta K Saldias Montivero, Fred W Kolling, Laurent Perrard, Lucas A Salas, Brock C Christensen, Thomas J Palys, Margaret R Karagas, Scott M Palisoul, Gregory J Tsongalis, Louis J Vaickus, Sarah M Preum, Joshua J Levy
{"title":"Potential to Enhance Large Scale Molecular Assessments of Skin Photoaging through Virtual Inference of Spatial Transcriptomics from Routine Staining.","authors":"Gokul Srinivasan, Matthew J Davis, Matthew R LeBoeuf, Michael Fatemi, Zarif L Azher, Yunrui Lu, Alos B Diallo, Marietta K Saldias Montivero, Fred W Kolling, Laurent Perrard, Lucas A Salas, Brock C Christensen, Thomas J Palys, Margaret R Karagas, Scott M Palisoul, Gregory J Tsongalis, Louis J Vaickus, Sarah M Preum, Joshua J Levy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The advent of spatial transcriptomics technologies has heralded a renaissance in research to advance our understanding of the spatial cellular and transcriptional heterogeneity within tissues. Spatial transcriptomics allows investigation of the interplay between cells, molecular pathways, and the surrounding tissue architecture and can help elucidate developmental trajectories, disease pathogenesis, and various niches in the tumor microenvironment. Photoaging is the histological and molecular skin damage resulting from chronic/acute sun exposure and is a major risk factor for skin cancer. Spatial transcriptomics technologies hold promise for improving the reliability of evaluating photoaging and developing new therapeutics. Challenges to current methods include limited focus on dermal elastosis variations and reliance on self-reported measures, which can introduce subjectivity and inconsistency. Spatial transcriptomics offers an opportunity to assess photoaging objectively and reproducibly in studies of carcinogenesis and discern the effectiveness of therapies that intervene in photoaging and preventing cancer. Evaluation of distinct histological architectures using highly-multiplexed spatial technologies can identify specific cell lineages that have been understudied due to their location beyond the depth of UV penetration. However, the cost and interpatient variability using state-of-the-art assays such as the 10x Genomics Spatial Transcriptomics assays limits the scope and scale of large-scale molecular epidemiologic studies. Here, we investigate the inference of spatial transcriptomics information from routine hematoxylin and eosin-stained (H&E) tissue slides. We employed the Visium CytAssist spatial transcriptomics assay to analyze over 18,000 genes at a 50-micron resolution for four patients from a cohort of 261 skin specimens collected adjacent to surgical resection sites for basal cell and squamous cell keratinocyte tumors. The spatial transcriptomics data was co-registered with 40x resolution whole slide imaging (WSI) information. We developed machine learning models that achieved a macro-averaged median AUC and F1 score of 0.80 and 0.61 and Spearman coefficient of 0.60 in inferring transcriptomic profiles across the slides, and accurately captured biological pathways across various tissue architectures.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"29 ","pages":"477-491"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10813837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075197","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}
Jacqueline A Piekos, Jeewoo Kim, Jacob M Keaton, Jacklyn N Hellwege, Todd L Edwards, Digna R Velez Edwards
{"title":"EVALUATING THE RELATIONSHIPS BETWEEN GENETIC ANCESTRY AND THE CLINICAL PHENOME.","authors":"Jacqueline A Piekos, Jeewoo Kim, Jacob M Keaton, Jacklyn N Hellwege, Todd L Edwards, Digna R Velez Edwards","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>There is a desire in research to move away from the concept of race as a clinical factor because it is a societal construct used as an imprecise proxy for geographic ancestry. 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 hypertension (HTN) and atrial fibrillation (AFib) to further investigate the relationships between these phenotypes and EAFR, WAFR, SEUR, and NEUR using logistic regression modeling and non-linear restricted cubic spline modeling (RCS). For EAS and SAS, we chose renal failure (RF) for further modeling. The relationships between HTN and AFib and the ancestries EAFR, WAFR, and SEUR were best fit by the linear model (beta p < 1x10-4 for all) while the relationships with NEUR were best fit with RCS (HTN ANOVA p = 0.001, AFib ANOVA p < 1x10-4). For RF, the relationship with SAS was best fit with a linear model (beta p < 1x10-4) while RCS model was a better fit for EAS (ANOVA p < 1x10-4). In this study, we identify relationships between genetic ancestry and phenotypes that are best fit with non-linear modeling techniques. The assumption of linearity for regression modeling is integral for proper fitting of a model and there is no knowing a priori to modeling if the relationship is truly linear.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"29 ","pages":"389-403"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075245","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}
Bao Hoang, Yijiang Pang, Hiroko H Dodge, Jiayu Zhou
{"title":"Subject Harmonization of Digital Biomarkers: Improved Detection of Mild Cognitive Impairment from Language Markers.","authors":"Bao Hoang, Yijiang Pang, Hiroko H Dodge, Jiayu Zhou","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mild cognitive impairment (MCI) represents the early stage of dementia including Alzheimer's disease (AD) and is a crucial stage for therapeutic interventions and treatment. Early detection of MCI offers opportunities for early intervention and significantly benefits cohort enrichment for clinical trials. Imaging and in vivo markers in plasma and cerebrospinal fluid biomarkers have high detection performance, yet their prohibitive costs and intrusiveness demand more affordable and accessible alternatives. The recent advances in digital biomarkers, especially language markers, have shown great potential, where variables informative to MCI are derived from linguistic and/or speech and later used for predictive modeling. A major challenge in modeling language markers comes from the variability of how each person speaks. As the cohort size for language studies is usually small due to extensive data collection efforts, the variability among persons makes language markers hard to generalize to unseen subjects. In this paper, we propose a novel subject harmonization tool to address the issue of distributional differences in language markers across subjects, thus enhancing the generalization performance of machine learning models. Our empirical results show that machine learning models built on our harmonized features have improved prediction performance on unseen data. The source code and experiment scripts are available at https://github.com/illidanlab/subject_harmonization.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"29 ","pages":"187-200"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075250","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}
Francisco M De La Vega, Kathleen C Barnes, Keolu Fox, Alexander Ioannidis, Eimear Kenny, Rasika A Mathias, Bogdan Pasaniuc
{"title":"Session Introduction: Overcoming health disparities in precision medicine.","authors":"Francisco M De La Vega, Kathleen C Barnes, Keolu Fox, Alexander Ioannidis, Eimear Kenny, Rasika A Mathias, Bogdan Pasaniuc","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The following sections are included:OverviewDealing with the lack of diversity in current research datasetsDevelopment of fair machine learning algorithmsRace, genetic ancestry, and population structureConclusionAcknowledgments.</p>","PeriodicalId":34954,"journal":{"name":"Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing","volume":"29 ","pages":"322-326"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075217","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}