Annual Review of Biomedical Data Science最新文献

While the primary sequences of human proteins have been cataloged for over a decade, determining how these are organized into a dynamic collection of multiprotein assemblies, with structures and functions spanning biological scales, is an ongoing venture. Systematic and data-driven analyses of these higher-order structures are emerging, facilitating the discovery and understanding of cellular phenotypes. At present, knowledge of protein localization and function has been primarily derived from manual annotation and curation in resources such as the Gene Ontology, which are biased toward richly annotated genes in the literature. Here, we envision a future powered by data-driven mapping of protein assemblies. These maps can capture and decode cellular functions through the integration of protein expression, localization, and interaction data across length scales and timescales. In this review, we focus on progress toward constructing integrated cell maps that accelerate the life sciences and translational research.

Alzheimer's disease (AD) is a critical national concern, affecting 5.8 million people and costing more than $250 billion annually. However, there is no available cure. Thus, effective strategies are in urgent need to discover AD biomarkers for disease early detection and drug development. In this review, we study AD from a biomedical data scientist perspective to discuss the four fundamental components in AD research: genetics (G), molecular multiomics (M), multimodal imaging biomarkers (B), and clinical outcomes (O) (collectively referred to as the GMBO framework). We provide a comprehensive review of common statistical and informatics methodologies for each component within the GMBO framework, accompanied by the major findings from landmark AD studies. Our review highlights the potential of multimodal biobank data in addressing key challenges in AD, such as early diagnosis, disease heterogeneity, and therapeutic development. We identify major hurdles in AD research, including data scarcity and complexity, and advocate for enhanced collaboration, data harmonization, and advanced modeling techniques. This review aims to be an essential guide for understanding current biomedical data science strategies in AD research, emphasizing the need for integrated, multidisciplinary approaches to advance our understanding and management of AD.

Overlaying omics data onto spatial biological dimensions has been a promising technology to provide high-resolution insights into the interactome and cellular heterogeneity relative to the organization of the molecular microenvironment of tissue samples in normal and disease states. Spatial omics can be categorized into three major modalities: (a) next-generation sequencing-based assays, (b) imaging-based spatially resolved transcriptomics approaches including in situ hybridization/in situ sequencing, and (c) imaging-based spatial proteomics. These modalities allow assessment of transcripts and proteins at a cellular level, generating large and computationally challenging datasets. The lack of standardized computational pipelines to analyze and integrate these nonuniform structured data has made it necessary to apply artificial intelligence and machine learning strategies to best visualize and translate their complexity. In this review, we summarize the currently available techniques and computational strategies, highlight their advantages and limitations, and discuss their future prospects in the scientific field.

The rapidly growing scale and variety of biomedical data repositories raise important privacy concerns. Conventional frameworks for collecting and sharing human subject data offer limited privacy protection, often necessitating the creation of data silos. Privacy-enhancing technologies (PETs) promise to safeguard these data and broaden their usage by providing means to share and analyze sensitive data while protecting privacy. Here, we review prominent PETs and illustrate their role in advancing biomedicine. We describe key use cases of PETs and their latest technical advances and highlight recent applications of PETs in a range of biomedical domains. We conclude by discussing outstanding challenges and social considerations that need to be addressed to facilitate a broader adoption of PETs in biomedical data science.

The integration of multiomics data with detailed phenotypic insights from electronic health records marks a paradigm shift in biomedical research, offering unparalleled holistic views into health and disease pathways. This review delineates the current landscape of multimodal omics data integration, emphasizing its transformative potential in generating a comprehensive understanding of complex biological systems. We explore robust methodologies for data integration, ranging from concatenation-based to transformation-based and network-based strategies, designed to harness the intricate nuances of diverse data types. Our discussion extends from incorporating large-scale population biobanks to dissecting high-dimensional omics layers at the single-cell level. The review underscores the emerging role of large language models in artificial intelligence, anticipating their influence as a near-future pivot in data integration approaches. Highlighting both achievements and hurdles, we advocate for a concerted effort toward sophisticated integration models, fortifying the foundation for groundbreaking discoveries in precision medicine.

Proteins on the surfaces of cells serve as physical connection points to bridge one cell with another, enabling direct communication between cells and cohesive structure. As biomedical research makes the leap from characterizing individual cells toward understanding the multicellular organization of the human body, the binding interactions between molecules on the surfaces of cells are foundational both for computational models and for clinical efforts to exploit these influential receptor pathways. To achieve this grander vision, we must assemble the full interactome of ways surface proteins can link together. This review investigates how close we are to knowing the human cell surface protein interactome. We summarize the current state of databases and systematic technologies to assemble surface protein interactomes, while highlighting substantial gaps that remain. We aim for this to serve as a road map for eventually building a more robust picture of the human cell surface protein interactome.

Disease trajectories, defined as sequential, directional disease associations, have become an intense research field driven by the availability of electronic population-wide healthcare data and sufficient computational power. Here, we provide an overview of disease trajectory studies with a focus on European work, including ontologies used as well as computational methodologies for the construction of disease trajectories. We also discuss different applications of disease trajectories from descriptive risk identification to disease progression, patient stratification, and personalized predictions using machine learning. We describe challenges and opportunities in the area that eventually will benefit from initiatives such as the European Health Data Space, which, with time, will make it possible to analyze data from cohorts comprising hundreds of millions of patients.

In the healthcare landscape, data science (DS) methods have emerged as indispensable tools to harness real-world data (RWD) from various data sources such as electronic health records, claim and registry data, and data gathered from digital health technologies. Real-world evidence (RWE) generated from RWD empowers researchers, clinicians, and policymakers with a more comprehensive understanding of real-world patient outcomes. Nevertheless, persistent challenges in RWD (e.g., messiness, voluminousness, heterogeneity, multimodality) and a growing awareness of the need for trustworthy and reliable RWE demand innovative, robust, and valid DS methods for analyzing RWD. In this article, I review some common current DS methods for extracting RWE and valuable insights from complex and diverse RWD. This article encompasses the entire RWE-generation pipeline, from study design with RWD to data preprocessing, exploratory analysis, methods for analyzing RWD, and trustworthiness and reliability guarantees, along with data ethics considerations and open-source tools. This review, tailored for an audience that may not be experts in DS, aspires to offer a systematic review of DS methods and assists readers in selecting suitable DS methods and enhancing the process of RWE generation for addressing their specific challenges.

Building longitudinal population cohorts in Africa for coordinated research and surveillance can influence the setting of national health priorities, lead to the introduction of appropriate interventions, and provide evidence for targeted treatment, leading to better health across the continent. However, compared to cohorts from the global north, longitudinal continental African population cohorts remain scarce, are relatively small in size, and lack data complexity. As infections and noncommunicable diseases disproportionately affect Africa's approximately 1.4 billion inhabitants, African cohorts present a unique opportunity for research and surveillance. High genetic diversity in African populations and multiomic research studies, together with detailed phenotyping and clinical profiling, will be a treasure trove for discovery. The outcomes, including novel drug targets, biological pathways for disease, and gene-environment interactions, will boost precision medicine approaches, not only in Africa but across the globe.

In clinical artificial intelligence (AI), graph representation learning, mainly through graph neural networks and graph transformer architectures, stands out for its capability to capture intricate relationships and structures within clinical datasets. With diverse data-from patient records to imaging-graph AI models process data holistically by viewing modalities and entities within them as nodes interconnected by their relationships. Graph AI facilitates model transfer across clinical tasks, enabling models to generalize across patient populations without additional parameters and with minimal to no retraining. However, the importance of human-centered design and model interpretability in clinical decision-making cannot be overstated. Since graph AI models capture information through localized neural transformations defined on relational datasets, they offer both an opportunity and a challenge in elucidating model rationale. Knowledge graphs can enhance interpretability by aligning model-driven insights with medical knowledge. Emerging graph AI models integrate diverse data modalities through pretraining, facilitate interactive feedback loops, and foster human-AI collaboration, paving the way toward clinically meaningful predictions.