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

The following sections are included: Overview, Background & key terms, Earth Friendly Computation 574: Indigenous Data Sovereignty, Circular Systems, and Solarpunk Solutions for a Sustainable Future, AI in Point-of-Care: A Sustainable Healthcare Revolution at the Edge, Conclusion: The Future of Earth Friendly Computation, Acknowledgments, References.

Precision medicine significantly enhances patients prognosis, offering personalized treatments. Particularly for metastatic cancer, incorporating primary tumor location into the diagnostic process greatly improves survival rates. However, traditional methods rely on human expertise, requiring substantial time and financial resources. To address this challenge, Machine Learning (ML) and Deep Learning (DL) have proven particularly effective. Yet, their application to medical data, especially genomic data, must consider and encompass privacy due to the highly sensitive nature of data. In this paper, we propose OGHE, a convolutional neural network-based approach for privacy-preserving cancer classification designed to exploit spatial patterns in genomic data, while maintaining confidentiality by means of Homomorphic Encryption (HE). This encryption scheme allows the processing directly on encrypted data, guaranteeing its confidentiality during the entire computation. The design of OGHE is specific for privacy-preserving applications, taking into account HE limitations from the outset, and introducing an efficient packing mechanism to minimize the computational overhead introduced by HE. Additionally, OGHE relies on a novel feature selection method, VarScout, designed to extract the most significant features through clustering and occurrence analysis, while preserving inherent spatial patterns. Coupled with VarScout, OGHE has been compared with existing privacy-preserving solutions for encrypted cancer classification on the iDash 2020 dataset, demonstrating their effectiveness in providing accurate privacy-preserving cancer classification, and reducing latency thanks to our packing mechanism. The code is released to the scientific community.

Given the rapidly expanding capabilities of generative AI models for radiology, there is a need for robust metrics that can accurately measure the quality of AI-generated radiology reports across diverse hospitals. We develop ReXamine-Global, a LLM-powered, multi-site framework that tests metrics across different writing styles and patient populations, exposing gaps in their generalization. First, our method tests whether a metric is undesirably sensitive to reporting style, providing different scores depending on whether AI-generated reports are stylistically similar to ground-truth reports or not. Second, our method measures whether a metric reliably agrees with experts, or whether metric and expert scores of AI-generated report quality diverge for some sites. Using 240 reports from 6 hospitals around the world, we apply ReXamine-Global to 7 established report evaluation metrics and uncover serious gaps in their generalizability. Developers can apply ReXamine-Global when designing new report evaluation metrics, ensuring their robustness across sites. Additionally, our analysis of existing metrics can guide users of those metrics towards evaluation procedures that work reliably at their sites of interest.

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.

Patients experiencing adverse drug events (ADE) from polypharmaceutical regimens present a huge challenge to modern healthcare. While computational efforts may reduce the incidence of these ADEs, current strategies are typically non-generalizable for standard healthcare systems. To address this, we carried out a retrospective study aimed at developing a statistical approach to detect and quantify potential ADEs. The data foundation comprised of almost 2 million patients from two health regions in Denmark and their drug and laboratory data during the years 2011 to 2016. We developed a series of multistate Cox models to compute hazard ratios for changes in laboratory test results before and after drug exposure. By linking the results to data from a drug-drug interaction database, we found that the models showed potential for applications for medical safety agencies and improved efficiency for drug approval pipelines.

There is a disconnect between data practices in biomedicine and public understanding of those data practices, and this disconnect is expanding rapidly every day (with the emergence of synthetic data and digital twins and more widely adopted Artificial Intelligence (AI)/Machine Learning tools). Transparency alone is insufficient to bridge this gap. Concurrently, there is an increasingly complex landscape of laws, regulations, and institutional/ programmatic policies to navigate when engaged in biocomputing and digital health research, which makes it increasingly difficult for those wanting to "get it right" or "do the right thing." Mandatory data protection obligations vary widely, sometimes focused on the type of data (and nuanced definition and scope parameters), the actor/entity involved, or the residency of the data subjects. Additional challenges come from attempts to celebrate biocomputing discoveries and digital health innovations, which frequently transform fair and accurate communications into exaggerated hype (e.g., to secure financial investment in future projects or lead to more favorable tenure and promotion decisions). Trust in scientists and scientific expertise can be quickly eroded if, for example, synthetic data is perceived by the public as "fake data" or if digital twins are perceived as "imaginary" patients. Researchers appear increasingly aware of the scientific and moral imperative to strengthen their work and facilitate its sustainability through increased diversity and community engagement. Moreover, there is a growing appreciation for the "data work" necessary to have scientific data become meaningful, actionable information, knowledge, and wisdom-not only for scientists but also for the individuals from whom those data were derived or to whom those data relate. Equity in the process of biocomputing and equity in the distribution of benefits and burdens of biocomputing both demand ongoing development, implementation, and refinement of embedded Ethical, Legal and Social Implications (ELSI) research practices. This workshop is intended to nurture interdisciplinary discussion of these issues and to highlight the skills and competencies all too often considered "soft skills" peripheral to other skills prioritized in traditional training and professional development programs. Data scientists attending this workshop will become better equipped to embed ELSI practices into their research.

Alzheimer's disease (AD), the predominant form of dementia, is influenced by several risk factors, including type 2 diabetes (T2D), a metabolic disorder characterized by the dysregulation of blood sugar levels. Despite mouse and human studies reporting this connection between T2D and AD, the mechanism by which T2D contributes to AD pathobiology is not well understood. A challenge in understanding mechanistic links between these conditions is that evidence between mouse and human experimental models must be synthesized, but translating between these systems is difficult due to evolutionary distance, physiological differences, and human heterogeneity. To address this, we employed a computational framework called translatable components regression (TransComp-R) to overcome discrepancies between pre-clinical and clinical studies using omics data. Here, we developed a novel extension of TransComp-R for multi-disease modeling to analyze transcriptomic data from brain samples of mouse models of AD, T2D, and simultaneous occurrence of both disease (ADxT2D) and postmortem human brain data to identify enriched pathways predictive of human AD status. Our TransComp-R model identified inflammatory and estrogen signaling pathways encoded by mouse principal components derived from models of T2D and ADxT2D, but not AD alone, predicted with human AD outcomes. The same mouse PCs predictive of human AD outcomes were able to capture sex-dependent differences in human AD biology, including significant effects unique to female patients, despite the TransComp-R being derived from data from only male mice. We demonstrated that our approach identifies biological pathways of interest at the intersection of the complex etiologies of AD and T2D which may guide future studies into pathogenesis and therapeutic development for patients with T2D-associated AD.

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.

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.

Functional brain networks represent dynamic and complex interactions among anatomical regions of interest (ROIs), providing crucial clinical insights for neural pattern discovery and disorder diagnosis. In recent years, graph neural networks (GNNs) have proven immense success and effectiveness in analyzing structured network data. However, due to the high complexity of data acquisition, resulting in limited training resources of neuroimaging data, GNNs, like all deep learning models, suffer from overfitting. Moreover, their capability to capture useful neural patterns for downstream prediction is also adversely affected. To address such challenge, this study proposes BrainSTEAM, an integrated framework featuring a spatio-temporal module that consists of an EdgeConv GNN model, an autoencoder network, and a Mixup strategy. In particular, the spatio-temporal module aims to dynamically segment the time series signals of the ROI features for each subject into chunked sequences. We leverage each sequence to construct correlation networks, thereby increasing the training data. Additionally, we employ the EdgeConv GNN to capture ROI connectivity structures, an autoencoder for data denoising, and mixup for enhancing model training through linear data augmentation. We evaluate our framework on two real-world neuroimaging datasets, ABIDE for Autism prediction and HCP for gender prediction. Extensive experiments demonstrate the superiority and robustness of BrainSTEAM when compared to a variety of existing models, showcasing the strong potential of our proposed mechanisms in generalizing to other studies for connectome-based fMRI analysis.