Search bioRxiv⌕ Search

Biology subjects

Yankovitz, G.

Publications and source records attributed to Yankovitz, G..

3 recordsLinked to original sources

GGE: General-purpose deep meta-learning for classification of human transcriptomes with limited data

Transcriptomic classification is often hindered by the small number of samples relative to the high dimensionality of gene expression data. We introduce General Gene Expression (GGE), a deep meta-learning framework designed to support robust classification in this limited-sample setting. By training across 5,220 distinct biomedical prediction objectives drawn from 1,779 different human datasets, GGE learns a model initialization that captures biological patterns shared across heterogeneous classification tasks. This learned initialization has two key advantages. First, it enables improved performance to new datasets using only a small number of labeled samples. Second, because it is learned across diverse prediction objectives, it can be applied to a broad range of biomedical problems. We show that GGE outperforms established classifiers in data-limited settings across a wide range of applications, including datasets generated using different RNA-seq platforms and preprocessing pipelines. In addition, attention-based analysis identifies recurrent genes that contribute to performance across multiple biological objectives, providing insight into shared determinants of human biological states. Together, these results establish GGE is a general-purpose framework for human transcriptome-based classification in biomedical settings where labeled data are scarce.

bioinformatics↗

The host transcriptional response to superinfection by influenza virus and streptococcus pneumonia

Secondary bacterial challenges during influenza virus infection ( superinfection) cause excessive mortality and hospitalization. Here we present a longitudinal study of gene-expression changes in murine lungs during superinfection, with an initial influenza A virus (IAV) infection and a subsequent Streptococcus pneumonia (SP) infection. In addition to the well-characterized impairment of the innate immune response, we identified superinfection-specific alterations in endothelial-related genes, including a previously uncharacterized rapid downregulation of particular angiogenic and vascular markers. Superinfection-specific alterations were also evident in the analysis of cellular states related to the hosts immune resistance against pathogens. We found that superinfected mice manifested an excessive rapid induction of immune resistance starting only a few hours after the secondary bacterial challenge. In addition, there was a substantial rewiring of the resistance program: interferon-regulated genes were switched from positive to negative correlations with resistance, whereas genes of fatty-acid metabolism were switched from negative to positive correlations with resistance. Thus, the transcriptional resistance state in superinfection is reprogrammed toward repressed interferon signaling and induced fatty acid metabolism. Our findings suggest new insights into the remodeling of the host defense upon superinfection, providing promising targets for future therapeutic interventions.

systems biology↗

Distinct gene programs underpinning 'disease tolerance' and 'resistance' in influenza virus infection

When challenged with an invading pathogen, the host defense response is engaged to eliminate the pathogen (resistance) and to maintain health in the presence of the pathogen (disease tolerance). However, the identification of distinct molecular programs underpinning disease tolerance and resistance remained obscure. We exploited transcriptional and physiological monitoring across 33 mouse strains, during in vivo influenza virus infection, to identify two host-defense gene programs - one is associated with hallmarks of disease tolerance and the other with hallmarks of resistance. Both programs constitute generic responses in multiple mouse and human cell types. Our study describes the organizational principles of these programs and validates Arhgdia as a regulator of disease-tolerance states in epithelial cells. We further reveal that the baseline disease-tolerance state in macrophages is associated with the pathophysiological response to injury and infection. Our framework provides a paradigm for the understanding of disease tolerance and resistance at the molecular level.

systems biology↗