RESUMO
The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability.
Assuntos
Catalogação/métodos , Biologia de Sistemas/métodos , Biologia Computacional/métodos , Bases de Dados de Compostos Químicos/normas , Perfilação da Expressão Gênica/métodos , Biblioteca Gênica , Humanos , Armazenamento e Recuperação da Informação/métodos , Programas Nacionais de Saúde , National Institutes of Health (U.S.)/normas , Transcriptoma , Estados UnidosRESUMO
We developed a model of 545 components (nodes) and 1259 interactions representing signaling pathways and cellular machines in the hippocampal CA1 neuron. Using graph theory methods, we analyzed ligand-induced signal flow through the system. Specification of input and output nodes allowed us to identify functional modules. Networking resulted in the emergence of regulatory motifs, such as positive and negative feedback and feedforward loops, that process information. Key regulators of plasticity were highly connected nodes required for the formation of regulatory motifs, indicating the potential importance of such motifs in determining cellular choices between homeostasis and plasticity.