BioSig: an informatics framework for representing the physiological responses of living cells

Progress in systems biology, systems physiology and physiomics has been recently reviewed [1–5]. In one example, detailed cellular models and cellular experiments were shown to play a crucial role in the successful construction of a whole-organ model of the heart [5]. The ability to trace genetic effects from abnormal protein function to cellular pathophysiology and then to organ abnormalities depended on a rich cellular dataset. Moreover, successful cell modeling in this example depended on the repeated interaction between simulation and the experimental dataset [5]. The BioSig (http://vision.lbl.gov/Projects/BioSig, http://vision.lbl.gov/Projects/vsom) imaging informatics system described here provides a framework for acquiring similar subcellular datasets for a variety of cell types. BioSig has been used for digital imaging studies of microscope specimens that have been sectioned, fixed and stained [6]. However, BioSig also contains features designed for realtime interaction with living cells across a distributed system. Such features facilitate the cataloging and analysis of subcellular, livingcell responses that are observed using digital imaging fluorescence microscopy. Advances in fluorescence microscopy and fluorescence-probe technologies have made it possible to collect responses of living cells across multiple channels of information [7,8]. BioSig has been designed to collect physiological responses together with experimental variables and the state of the instrument. Large amounts of multichannel spatio-temporal data are effectively represented in BioSig for further analysis, manipulation and remote access. The effective representation of these data enables dynamic microscope control for online studies while simultaneously making these representations accessible through the Internet. Visual-servoing optical microscopy (VSOM) protocols and instrumentation accomplish real-time interactions with living cells by repeatedly performing the following steps: (1) perturbation or stimulation of cells (immobilized on a surface in a perfusion chamber) via computer-controlled syringe pumps; (2) analysis of the resultant physiological responses of individual cells and organelles; and (3) adjustment of pump operation based on observed cell responses and previously archived cell responses [9]. The BioSig framework is designed to make the richly annotated cell responses of previous VSOM experiments available during this process. In this way, instrument control can be knowledge based because decisions can be made by referring to archived cell responses obtained under similar experimental conditions. In addition, instrument control can be adaptive, because perturbations are adjusted based on observed cell responses, or cell simulations running interactively or in parallel with on-line VSOM experiments. Such a coupling BioSig: an informatics framework for representing the physiological responses of living cells Bahram Parvin and Daniel E. Callahan