The Jackson Laboratory Senescence Tissue Mapping Center (JAX-Sen TMC) - Data Analysis Core

点击翻译按钮获取中文摘要

PROJECT SUMMARY/ABSTRACT DATA ANALYSIS CORE The objective of the Data Analysis Core (DAC) of the JAX-Sen mouse Tissue Mapping Center (TMC) is to construct biomarker datasets and molecular maps of cellular senescence in mice and deliver these data to the SenNet Consortium Organization and Data Coordinating Center (CODCC). The Biological Analysis Core (BAC) of JAX-Sen will generate high-resolution, high-content molecular data to characterize cellular senescence in mouse kidney, adipose tissue, pancreas, placenta, heart and hypothalamus in aged, inbred and genetically diverse mouse cohorts. From these data, the DAC will establish state-of-the-art workflows for data annotation, curation, and analysis of transcriptomic, imaging, and imaging mass spectrometry (IMS) data to build cellular senescence maps. The DAC will collaborate closely with the DAC of the human SenNet TMC at JAX and UConn Health (KAPP-Sen TMC), other human and mouse TMCs and the CODCC to develop and implement Network- wide standards for processing, analyzing and visualizing SenNet data. The JAX-Sen DAC will leverage significant recent advances in deep learning and computer vision to define robust biomarkers of senescent cells and map their tissue context. To achieve its goals, the JAX-Sen DAC will implement rigorous and reproducible data annotation, curation, processing, and dissemination (Aim 1). The DAC will receive and centralize sequencing, imaging, and IMS data from the JAX-Sen BAC. It will automate and harden QC procedures to screen for annotation and curation errors, batch effects, and low-quality samples in collaboration with the BAC. The DAC will implement the pipelines based on common community standards, benchmark on JAX-Sen and reference datasets, and then containerize for sharing with the CODCC. From these data, the JAX-Sen DAC will construct biomarker datasets and molecular maps of cellular senescence (Aim 2). The DAC will deploy analysis pipelines for sequencing, image and IMS data with known and prospective senescence markers to identify and functionally annotate novel biomarkers of senescent cells and map their tissue context, compute the diversity within senescent cell populations, and quantify cell-to-cell interactions between senescent cells and neighboring cells. The DAC will aggregate and integrate these data and metadata to build high-quality maps of cellular senescence. Finally, the JAX-Sen DAC will disseminate JAX-Sen data with rigorous and reproducible open- source processing pipelines (Aim 3). The DAC will harmonize, standardize, and disseminate data processing and analytic pipelines with the CODCC, adhering to common community standards, standard operating procedures, and the network data sharing policy to exact reproducibility. We will collaborate with KAPP-Sen and other CODCC projects and TMCs to identify synergy, e.g., align human and mouse biomarkers on the same tissues.