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Katja Nowick

Publications and source records attributed to Katja Nowick.

3 recordsLinked to original sources

GCnet: Using Granger causality to explore the dynamic causality relations among genes as-sociated with intellectual disability in human brain

Intellectual disability (ID) is defined by an IQ under 70, in addition to deficits in two or more adaptive behaviors that affect everyday living. Throughout history, individuals with ID have often been margin-alized from society and continue to suffer significantly even in modern times. A varying proportion of ID cases are attributable to genetic causes. Identifying the causal relation among these ID-associated genes and their gene expression pattern during brain development process would gain us a better understanding of the molecular basis of ID. In this paper, we interpret gene expression data collected at different time points during the in vitro brain development process as time series and further introduce Granger causality test to evaluate the dynamic dependence relations among genes. These evaluations are used as input to construct gene expression network and extract the pathological information associated to ID including identi-fying new genes that can be critically related to the disease. To demonstrate our methods, we pro-vide a priority list of new genes that are most likely associated with Mowat Wilson Syndrome via monitoring the community structure of ZEB2 in our Granger causality network constructed based on the Kutsche dataset (Kutsche, et al., 2018).

q-bio.MN

Comparing multiple networks using the Co-expression Differential Network Analysis (CoDiNA)

Biomedical sciences are increasingly recognising the relevance of gene co-expression-networks for analysing complex-systems, phenotypes or diseases. When the goal is investigating complex-phenotypes under varying conditions, it comes naturally to employ comparative network methods. While approaches for comparing two networks exist, this is not the case for multiple networks. Here we present a method for the systematic comparison of an unlimited number of networks: Co-expression Differential Network Analysis (CoDiNA) for detecting links and nodes that are common, specific or different to the networks. Applying CoDiNA to a neurogenesis study identified genes for neuron differentiation. Experimentally overexpressing one candidate resulted in significant disturbance in the underlying neurogenesis' gene regulatory network. We compared data from adults and children with active tuberculosis to test for signatures of HIV. We also identified common and distinct network features for particular cancer types with CoDiNA. These studies show that CoDiNA successfully detects genes associated with the diseases.

stat.CO

wTO: an R package for computing weighted topological overlap and consensus networks with an integrated visualization tool

Network analyses, such as of gene co-expression networks, metabolic networks and ecological networks have become a central approach for the systems-level study of biological data. Several software packages exist for generating and analyzing such networks, either from correlation scores or the absolute value of a transformed score called weighted topological overlap (wTO). However, since gene regulatory processes can up- or down-regulate genes, it is of great interest to explicitly consider both positive and negative correlations when constructing a gene co-expression network. Here, we present an R package for calculating the wTO, that, in contrast to existing packages, explicitly addresses the sign of the wTO values, and is thus especially valuable for the analysis of gene regulatory networks. The package includes the calculation of p-values (raw and adjusted) for each pairwise gene score. Our package also allows the calculation of networks from time series (without replicates). Since networks from independent datasets (biological repeats or related studies) are not the same due to technical and biological noise in the data, we additionally, incorporated a novel method for calculating a consensus network (CN) from two or more networks into our R package. We compare our new wTO package to state of art packages and demonstrate the application of the wTO and CN functions using 3 independently derived datasets from healthy human pre-frontal cortex samples. To showcase an example for the time series application we utilized a metagenomics data set. In this work, we developed a software package that allows the computation of wTO networks, CNs and a visualization tool in the R statistical environment. It is publicly available on CRAN repositories under the GPL-2 Open Source License (https://cran.r-project.org/web/packages/wTO/).

q-bio.MN