ABSTRACT
A number of high-content technologies allow deriving what is nowadays often called “big data” from cellular models. The challenge is to make “big sense” from “big data.” Toxicology with its challenges (Hartung 2009) is used as a prime example here. The main opportunity is to deduce the underlying adverse outcome pathways, i.e., the pathways of toxicity and disease manifestations. However, in order to understand aspects of these processes and possible perturbations in disease or due to toxic or traumatic insults, it is necessary to make such cell models available. It is not about “big data” but about “good big data” and this starts with good cell models. With the
5.1 Introduction ....................................................................................................85 5.2 Organotypic Cell Culture ...............................................................................86 5.3 Sources of Cells for 3D Cultures ....................................................................88 5.4 Better Cell Systems also Need Better Quality Assurance ..............................88 5.5 The Use of Omics Technologies for Pathway Mapping and
Toxicological Testing Strategies ..................................................................... 91 5.5.1 Each Omics is Different .....................................................................92 5.5.2 A Model Does not Become Better by Adding Fancy
Omics Endpoint ..................................................................................93 5.5.3 The Problem is not in Generating but Interpreting Data-The
Signal vs. Noise Problem and Signatures of Toxicity ........................94 5.5.4 Biomarkers of Mechanism Promise to “Clean” Signatures of
Toxicity and Make Them Translatable Between Model Systems .......94 5.5.5 The Challenge of Pathway of Toxicity Identification and Annotation ..... 95 5.5.6 The Challenge of PoT Qualification ...................................................95 5.5.7 The Challenge of Strategically Integrating Multiple Tests .................95 5.5.8 The Goal of Systems Toxicology ........................................................96
