Statistical Inference and Reverse Engineering of Gene Regulatory Networks from Observational Expression Data

In this paper, we present a systematic and conceptual overview of methods for inferring gene regulatory networks from observational gene expression data. Further, we discuss two classic approaches to infer causal structures and compare them with contemporary methods by providing a conceptual categorization thereof. We complement the above by surveying global and local evaluation measures for assessing the performance of inference algorithms

Enhancing systems medicine beyond genotype data]{Enhancing systems medicine beyond genotype data by dynamic patient signatures: Having information and using it too

In order to establish systems medicine, based on the results and insights from basic biological research applicable for a medical and a clinical patient care, it is essential to measure patient-based data that represent the molecular and cellular state of the patient's pathology. In this paper, we discuss potential limitations of the sole usage of static genotype data, e.g., from next-generation sequencing, for translational research. The hypothesis advocated in this paper is that dynOmics data, i.e., high-throughput data that are capable of capturing dynamic aspects of the activity of samples from patients, are important for enabling personalized medicine by complementing genotype data

Untangling statistical and biological models to understand network inference: The need for a genomics network ontology

In this paper, we shed light on approaches that are currently used to infer networks from gene expression data with respect to their biological meaning. As we will show, the biological interpretation of these networks depends on the chosen theoretical perspective. For this reason, we distinguish a {it statistical perspective} from a {it mathematical modeling perspective} and elaborate their differences and implications. Our results indicate the imperative need for a {it genomic network ontology} in order to avoid increasing confusion about the biological interpretation of inferred networks, which can be even enhanced by approaches that integrate multiple data sets, respectively, data types

The gene regulatory network for breast cancer: Integrated regulatory landscape of cancer hallmarks

In this study, we infer the breast cancer gene regulatory network from gene expression data. This network is obtained from the application of the BC3Net inference algorithm to a large-scale gene expression data set consisting of $351$ patient samples. In order to elucidate the functional relevance of the inferred network, we are performing a Gene Ontology (GO) analysis for its structural components. Our analysis reveals that most significant GO-terms we find for the breast cancer network represent functional modules of biological processes that are described by known cancer hallmarks, including translation, immune response, cell cycle, organelle fission, mitosis, cell adhesion, RNA processing, RNA splicing and response to wounding. Furthermore, by using a curated list of census cancer genes, we find an enrichment in these functional modules. Finally, we study cooperative effects of chromosomes based on information of interacting genes in the beast cancer network. We find that chromosome $21$ is most coactive with other chromosomes. To our knowledge this is the first study investigating the genome-scale breast cancer network

Relevance of different prior knowledge sources for inferring gene interaction networks

When inferring networks from high-throughput genomic data, one of the main challenges is the subsequent validation of these networks. In the best case scenario, the true network is partially known from previous research results published in structured databases or research articles. Traditionally, inferred networks are validated against these known interactions. Whenever the recovery rate is gauged to be high enough, subsequent high scoring but unknown inferred interactions are deemed good candidates for further experimental validation. Therefore such validation framework strongly depends on the quantity and quality of published interactions and presents serious pitfalls: (I) availability of these known interactions for the studied problem might be sparse; (II) quantitatively comparing different inference algorithms is not trivial; and (III) the use of these known interactions for validation prevents their integration in the inference procedure. The latter is particularly relevant as it has recently been showed that integration of priors during network inference significantly improves the quality of inferred networks. To overcome these problems when validating inferred networks, we recently proposed a data-driven validation framework based on single gene knock-down experiments. Using this framework, we were able to demonstrate the benefits of integrating prior knowledge and expression data. In this paper we used this framework to assess the quality of different sources of prior knowledge on their own and in combination with different genomic datasets in colorectal cancer. We observed that most prior sources lead to significant F-scores. Furthermore, their integration with genomic data leads to a significant increase in F-scores, especially for priors extracted from full text PubMed articles, known co-expression modules and genetic interactions. Lastly, we observed that the results are consistent for three different datasets