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

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.

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.

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.

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.

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.

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.

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.

Polygenic risk scores (PRS) have predominantly been derived from genome-wide association studies (GWAS) conducted in European ancestry (EUR) individuals. In this study, we present an in-depth evaluation of PRS based on multi-ancestry GWAS for five cardiometabolic phenotypes in the Penn Medicine BioBank (PMBB) followed by a phenome-wide association study (PheWAS). We examine the PRS performance across all individuals and separately in African ancestry (AFR) and EUR ancestry groups. For AFR individuals, PRS derived using the multi-ancestry LD panel showed a higher effect size for four out of five PRSs (DBP, SBP, T2D, and BMI) than those derived from the AFR LD panel. In contrast, for EUR individuals, the multi-ancestry LD panel PRS demonstrated a higher effect size for two out of five PRSs (SBP and T2D) compared to the EUR LD panel. These findings underscore the potential benefits of utilizing a multi-ancestry LD panel for PRS derivation in diverse genetic backgrounds and demonstrate overall robustness in all individuals. Our results also revealed significant associations between PRS and various phenotypic categories. For instance, CAD PRS was linked with 18 phenotypes in AFR and 82 in EUR, while T2D PRS correlated with 84 phenotypes in AFR and 78 in EUR. Notably, associations like hyperlipidemia, renal failure, atrial fibrillation, coronary atherosclerosis, obesity, and hypertension were observed across different PRSs in both AFR and EUR groups, with varying effect sizes and significance levels. However, in AFR individuals, the strength and number of PRS associations with other phenotypes were generally reduced compared to EUR individuals. Our study underscores the need for future research to prioritize 1) conducting GWAS in diverse ancestry groups and 2) creating a cosmopolitan PRS methodology that is universally applicable across all genetic backgrounds. Such advances will foster a more equitable and personalized approach to precision medicine.

Founded nearly 30 years ago, the Pacific Symposium on Biocomputing (PSB) has continually promoted collaborative research in computational biology, annually highlighting emergent themes that reflect the expanding interdisciplinary nature of the field. This study aimed to explore the collaborative and thematic dynamics at PSB using topic modeling and network analysis methods. We identified 14 central topics that have characterized the discourse at PSB over the past three decades. Our findings demonstrate significant trends in topic relevance, with a growing emphasis on machine learning and integrative analyses. We observed not only an expanding nexus of collaboration but also PSB's crucial role in fostering interdisciplinary collaborations. It remains unclear, however, whether the shift towards interdisciplinarity was driven by the conference itself, external academic trends, or broader societal shifts towards integrated research approaches. Future applications of next-generation analytical methods may offer deeper insights into these dynamics. Additionally, we have developed a web application that leverages retrieval augmented generation and large language models, enabling users to efficiently explore past PSB proceedings.

Accurate prediction of suicide risk is crucial for identifying patients with elevated risk burden, helping ensure these patients receive targeted care. The US Department of Veteran Affairs' suicide prediction model primarily leverages structured electronic health records (EHR) data. This approach largely overlooks unstructured EHR, a data format that could be utilized to enhance predictive accuracy. This study aims to enhance suicide risk models' predictive accuracy by developing a model that incorporates both structured EHR predictors and semantic NLP-derived variables from unstructured EHR. XGBoost models were fit to predict suicide risk- the interactions identified by the model were extracted using SHAP, validated using logistic regression models, added to a ridge regression model, which was subsequently compared to a ridge regression approach without the use of interactions. By introducing a selection parameter, α, to balance the influence of structured (α=1) and unstructured (α=0) data, we found that intermediate α values achieved optimal performance across various risk strata, improved model performance of the ridge regression approach and uncovered significant cross-modal interactions between psychosocial constructs and patient characteristics. These interactions highlight how psychosocial risk factors are influenced by individual patient contexts, potentially informing improved risk prediction methods and personalized interventions. Our findings underscore the importance of incorporating nuanced narrative data into predictive models and set the stage for future research that will expand the use of advanced machine learning techniques, including deep learning, to further refine suicide risk prediction methods.