Development and application of pediatric-specific blood transcriptional modules across diverse geographical settings through public data mining

/Abstract Blood transcriptional modules (BTMs), consisting of functionally related gene sets developed through dimensional reduction computational methods, have emerged as a significant tool for the biological interpretation of bulk transcriptomic data. However, current BTMs, primarily derived from North American and European adult data, fail to capture the immunological characteristics of pediatric populations across diverse geographical settings. To address this significant gap, we aim to develop pediatric-specific BTMs (pBTMs) that capture the broad range of heterogeneous physiological states during childhood and include underrepresented pediatric geographical cohorts through public data mining. For this purpose, we will construct modules utilizing transcriptome data from children aged birth to 12 years. We have gathered 13,388 samples from 76 studies across various physiological conditions, enabling the construction of robust and widely applicable pediatric- specific modules. This work will be the first to establish pediatric-specific BTMs, serving as a valuable resource for pediatric immunology research and empowering the development of vaccines and therapies to reduce the burden of infections and other immune-mediated diseases in childhood. This project also aims to address several limitations of previous frameworks by incorporating an improved a priori knowledge base using pediatric single- cell datasets and an assessment framework for the biological relevance of the pBTMs using genome-wide association studies (GWAS). Our state-of-the-art and novel computational framework will be delivered as a portable, version-controlled, publicly available pipeline that can be replicated in other disease and tissue type settings. To demonstrate the utility of pBTMs and as a proof of concept, we will utilize these modules to define immunological differences across geographically disparate pediatric populations, informing research into variability in childhood immune responses. Project Number: 1R21AI191085-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: Thomas Hagan | Institution: CINCINNATI CHILDRENS HOSP MED CTR, CINCINNATI, OH | Award Amount: $286,791 | Activity Code: R21 | Study Section: Population based Research in Infectious Disease Study Section[PRID] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R21AI19108501