Cross-species Conservation of context-specific networks

Abstract

BackgroundMany large data compendia on context-specific high-throughput genomic and regulatory data have been made available by international research consortia such as ENCODE, TCGA, and Epigenomics Roadmap. The use of these resources is impaired by the sheer size of the available big data and big metadata. Many of these context-specific data can be modeled as data derived regulatory networks (DDRNs) representing the complex and complicated interactions between transcription factors and target genes. These DDRNs are useful for the understanding of regulatory mechanisms and helpful for interpreting biomedical data.ResultsThe Cross-species Conservation framework (CroCo) provides a network-oriented view on the ENCODE regulatory data (CroCo network repository), convenient ways to access and browse networks and metadata, and a method to combine networks across compendia, experimental techniques, and species (CroCo tool suite). DDRNs can be combined with additional information and networks derived from the literature, curated resources, and computational predictions in order to enable detailed exploration and cross checking of regulatory interactions. Applications of the CroCo framework range from simple evidence look-up for user-defined regulatory interactions to the identification of conserved sub-networks in diverse cell-lines, conditions, and even species.ConclusionCroCo adds an intuitive unifying view on the data from the ENCODE projects via a comprehensive repository of derived context-specific regulatory networks and enables flexible cross-context, cross-species, and cross-compendia comparison via a basis set of analysis tools.The CroCo web-application and Cytoscape plug-in are freely available at: http://services.bio.ifi.lmu.de/croco-web. The web-page links to a detailed system description, a user guide, and tutorial videos presenting common use cases of the CroCo framework.

<p>Association study of the excitatory amino acid transporter 2 (EAAT2) and glycine transporter 1 (GlyT1) gene polymorphism with schizophrenia in a Polish population</p>

“…Some authors highlight greater severity of negative symptoms of schizophrenia in men and affective and positive symptoms in women. There is also evidence of gender differences in gene expression in the PFC of schizophrenia patients 52. We analyzed the effect of gender and genotype of the −181 A/C polymorphism on the age of onset in the schizophrenia group.…”

Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health

“…More specific to AD, TMAO has also been shown to restore the ability of mutant tau protein to promote microtubule assembly 61,62 with microtubule disassembly and neuron death being hallmark pathological features of AD. 63 In addition to its potential use as an AD biomarker, 64 TMAO may also have a therapeutic effect in AD and other protein-misfolding conditions, by preferentially hydrating partially denatured proteins to correct folding defects and entropically stabilizing native conformations. 65,66 Amino acid metabolites: the gut microbiota plays an essential role in amino acid catabolism the products of which can influence the balance between the production of excitatory and inhibitory neurotransmitters essential for correct brain functioning.…”

Evaluating Transcription Factor Activity Changes by Scoring Unexplained Target Genes in Expression Data

“…The human gene regulatory network is much larger and more complex than the yeast regulatory network. [ 20 ] To demonstrate and evaluate our approach on human data, we constructed a context-specific network from DNase I hypersensitivity and ChIPseq data for two ENCODE cell lines [ 21 , 22 ] and experimentally validated miRNA-target regulations [ 23 ]. The resulting network was used to find the active TFs which yield the minimal i-score for the RNAseq data of the corresponding cell lines.…”