SP12 - Quality management & Standards

S. Wiemann, Ute Ernst, Anja Irsigler (DKFZ)

The overall goal of this subproject is to overview the experimental projects of IG-CSG and to provide support in QM & Standards. Along these lines, quality control has been implemented as a prerequisite for the subsequent utilization of the diverse types of data obtained in IG-CSG, and standardization issues foster the robustness and reproducibility of experiments.

The subprojects of IG-CSG synergistically work on the same biomedical focus area, generating and delivering complementary data and information that is employed in a systems genomics modeling of pathways and networks towards the identification of novel therapeutic targets. The impact of IG-CSG strictly depends on the relevance and quality of the underlying data, and thus necessitates a tight quality control that further requires the establishment and adoption of standardized work flows. There, high-throughput technologies demand a special focus on quality measures in order to permit a systematic exploitation and integration of resulting data. Specific means are devised to tackle, for example, the “multiple testing problem”, the robustness of functional cellular assays, and the standardized annotation of resulting data and information. The QM & Standards subproject advises and follows the experimental subprojects, and devises and implements efficient strategies towards quality controlled data generation and standardized data management and description. The QM & Standards subproject is thus one key element of IG-CSG which connects to all other subprojects. 

Statistical power analysis of screen. The number of replicates that is required to be experimentally tested in order to achieve a true difference in the means (at p=0.005) is given. This analysis was done in preparation of a large screen in SP3 - and resulted in the number of replicates to be set to 4.

Several screening technologies (high-content screening microscopy, xCELLigence) and cell based assays (e.g., automated wound-healing scratch assay, impedance real-time assay) have been newly implemented in IG-CSG within the past two years. These enhancements in the spectrum of applications necessitated several developments in quality control (e.g., learning about the strengths and limitations of the individual data acquisition technologies [e.g., impact of different cellular phenotypes on the output of xCELLigence instrument], optimization of hardware in close relation with the respective hardware suppliers [e.g., hardware autofocus, pipetting device as well as temperature/humidity control of ScanR high-content screening microscope], adaptation of low-throughput assays to automated settings [e.g., optimization of scratch conditions in wound-healing assay for robotic 96well tool and glass-bottom plates], testing of reproducibility and robustness of assays <-> optimization and validation of controls [e.g., selection of strong and weak positive controls to test the dynamic range of assays; testing different combinations of tips and plates for reproducible scratching of cell lawns], establishing experimental parameters critical for the successful application of technologies and assays [e.g., testing different times of perturbation until the end-point assay to optimize the content of data]).