Annual Review of Biomedical Data Science最新文献

Single-cell RNA sequencing methods have led to improved understanding of the heterogeneity and transcriptomic states present in complex biological systems. Recently, the development of novel single-cell technologies for assaying additional modalities, specifically genomic, epigenomic, proteomic, and spatial data, allows for unprecedented insight into cellular biology. While certain technologies collect multiple measurements from the same cells simultaneously, even when modalities are separately assayed in different cells, we can apply novel computational methods to integrate these data. The application of computational integration methods to multimodal paired and unpaired data results in rich information about the identities of the cells present and the interactions between different levels of biology, such as between genetic variation and transcription. In this review, we both discuss the single-cell technologies for measuring these modalities and describe and characterize a variety of computational integration methods for combining the resulting data to leverage multimodal information toward greater biological insight.

Polygenic risk scores (PRS) estimate an individual's genetic likelihood of complex traits and diseases by aggregating information across multiple genetic variants identified from genome-wide association studies. PRS can predict a broad spectrum of diseases and have therefore been widely used in research settings. Some work has investigated their potential applications as biomarkers in preventative medicine, but significant work is still needed to definitively establish and communicate absolute risk to patients for genetic and modifiable risk factors across demographic groups. However, the biggest limitation of PRS currently is that they show poor generalizability across diverse ancestries and cohorts. Major efforts are underway through methodological development and data generation initiatives to improve their generalizability. This review aims to comprehensively discuss current progress on the development of PRS, the factors that affect their generalizability, and promising areas for improving their accuracy, portability, and implementation.

Genomics data are important for advancing biomedical research, improving clinical care, and informing other disciplines such as forensics and genealogy. However, privacy concerns arise when genomic data are shared. In particular, the identifying nature of genetic information, its direct relationship to health status, and the potential financial harm and stigmatization posed to individuals and their blood relatives call for a survey of the privacy issues related to sharing genetic and related data and potential solutions to overcome these issues. In this work, we provide an overview of the importance of genomic privacy, the information gleaned from genomics data, the sources of potential private information leakages in genomics, and ways to preserve privacy while utilizing the genetic information in research. We discuss the relationship between trust in the scientific community and protecting privacy, illuminating a future roadmap for data sharing and study participation.

One goal of genomic medicine is to uncover an individual's genetic risk for disease, which generally requires data connecting genotype to phenotype, as done in genome-wide association studies (GWAS). While there may be clinical promise to employing prediction tools such as polygenic risk scores (PRS), it currently stands that individuals of non-European ancestry may not reap the benefits of genomic medicine because of underrepresentation in large-scale genetics studies. Here, we discuss why this inequity poses a problem for genomic medicine and the reasons for the low transferability of PRS across populations. We also survey the ancestry representation of published GWAS and investigate how estimates of ancestry diversity in GWASparticipants might be biased. We highlight the importance of expanding genetic research in Africa, one of the most underrepresented regions in human genomics research, and discuss issues of ethics, resources, and technology for equitable advancement of genomic medicine.

The formation of protein complexes is crucial to most biological functions. The cellular mechanisms governing protein complex biogenesis are not yet well understood, but some principles of cotranslational and posttranslational assembly are beginning to emerge. In bacteria, this process is favored by operons encoding subunits of protein complexes. Eukaryotic cells do not have polycistronic mRNAs, raising the question of how they orchestrate the encounter of unassembled subunits. Here we review the constraints and mechanisms governing eukaryotic co- and posttranslational protein folding and assembly, including the influence of elongation rate on nascent chain targeting, folding, and chaperone interactions. Recent evidence shows that mRNAs encoding subunits of oligomeric assemblies can undergo localized translation and form cytoplasmic condensates that might facilitate the assembly of protein complexes. Understanding the interplay between localized mRNA translation and cotranslational proteostasis will be critical to defining protein complex assembly in vivo.

statistics for genome-wide association studies (GWAS) are increasingly available for downstream analyses. Meanwhile, the popularity of causal inference methods has grown as we look to gather robust evidence for novel medical and public health interventions. This has led to the development of methods that use GWAS summary statistics for causal inference. Here, we describe these methods in order of their escalating complexity, from genetic associations to extensions of Mendelian randomization that consider thousands of phenotypes simultaneously. We also cover the assumptions and limitations of these approaches before considering the challenges faced by researchers performing causal inference using GWAS data. GWAS summary statistics constitute an important data source for causal inference research that offers a counterpoint to nongenetic methods when triangulating evidence. Continued efforts to address the challenges in using GWAS data for causal inference will allow the full impact of these approaches to be realized.

A bias in health research to favor understanding diseases as they present in men can have a grave impact on the health of women. This paper reports on a conceptual review of the literature on machine learning or natural language processing (NLP) techniques to interrogate big data for identifying sex-specific health disparities. We searched Ovid MEDLINE, Embase, and PsycINFO in October 2021 using synonyms and indexing terms for (a) "women," "men," or "sex"; (b) "big data," "artificial intelligence," or "NLP"; and (c) "disparities" or "differences." From 902 records, 22 studies met the inclusion criteria and were analyzed. Results demonstrate that the inclusion by sex is inconsistent and often unreported, although the inclusion of men in these studies is disproportionately less than women. Even though artificial intelligence and NLP techniques are widely applied in healthresearch, few studies use them to take advantage of unstructured text to investigate sex-related differences or disparities. Researchers are increasingly aware of sex-based data bias, but the process toward correction is slow. We reflect on best practices on using big data analytics to address sex-specific biases in understanding the etiology, diagnosis, and prognosis of diseases.