Abstract
BackgroundConsideration of tissue-specific gene expression in reconstruction and analysis of molecular genetic networks is necessary for a proper description of the processes occurring in a specified tissue. Currently, there are a number of computer systems that allow the user to reconstruct molecular-genetic networks using the data automatically extracted from the texts of scientific publications. Examples of such systems are STRING, Pathway Commons, MetaCore and Ingenuity. The MetaCore and Ingenuity systems permit taking into account tissue-specific gene expression during the reconstruction of gene networks. Previously, we developed the ANDSystem tool, which also provides an automated extraction of knowledge from scientific texts and allows the reconstruction of gene networks. The main difference between our system and other tools is in the different types of interactions between objects, which makes the ANDSystem complementary to existing well-known systems. However, previous versions of the ANDSystem did not contain any information on tissue-specific expression.ResultsA new version of the ANDSystem has been developed. It offers the reconstruction of associative gene networks while taking into account the tissue-specific gene expression. The ANDSystem knowledge base features information on tissue-specific expression for 272 tissues. The system allows the reconstruction of combined gene networks, as well as performing the filtering of genes from such networks using the information on their tissue-specific expression. As an example of the application of such filtering, the gene network of the extrinsic apoptotic signaling pathway was analyzed. It was shown that considering different tissues can lead to changes in gene network structure, including changes in such indicators as betweenness centrality of vertices, clustering coefficient, network centralization, network density, etc.ConclusionsThe consideration of tissue specificity can play an important role in the analysis of gene networks, in particular solving the problem of finding the most significant central genes. Thus, the new version of ANDSystem can be employed for a wide range of tasks related to biomedical studies of individual tissues. It is available at http://www-bionet.sscc.ru/and/cell/.
Highlights
Consideration of tissue-specific gene expression in reconstruction and analysis of molecular genetic networks is necessary for a proper description of the processes occurring in a specified tissue
The consideration of tissue specificity can play an important role in the analysis of gene networks, in particular solving the problem of finding the most significant central genes
The new version of ANDSystem can be employed for a wide range of tasks related to biomedical studies of individual tissues
Summary
Consideration of tissue-specific gene expression in reconstruction and analysis of molecular genetic networks is necessary for a proper description of the processes occurring in a specified tissue. There are a number of computer systems that allow the user to reconstruct molecular-genetic networks using the data automatically extracted from the texts of scientific publications. The integration of information in knowledge bases with its further analysis can allow the generation of new hypotheses and obtaining novel knowledge about complex processes or mechanisms based on information about the individual subsystems that are part of such processes This allows the reconstruction of the molecular genetic mechanisms of the functioning of living systems, which is a necessary condition for study of almost any important task in modern biology and biomedicine, including the search for drug targets, an assessment of the potential efficacy and toxicity of new drugs in pre-clinical trials, identification of biomarker molecules to create effective diagnostic systems, the search for candidate genes for genotyping, etc. This allows the reconstruction of the molecular genetic mechanisms of the functioning of living systems, which is a necessary condition for study of almost any important task in modern biology and biomedicine, including the search for drug targets, an assessment of the potential efficacy and toxicity of new drugs in pre-clinical trials, identification of biomarker molecules to create effective diagnostic systems, the search for candidate genes for genotyping, etc. [2]
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