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*Search for genes, compounds, disease, cell/cell lines, organ, disease, pathway, process. (E.g CDK5)
About NetPro™
NetPro™ developed at Molecular Connections, offers solutions for the pharmaceutical and life sciences industries/researchers to streamline and speed up the drug discovery process.
NetPro™ Application Areas:
Custom curation
Expert Curation & Analysis Services are scientific services that can help expedite your research programs. The key value proposition is to leverage the ability to interpret and analyze your organization's research/experimental data and correlate it with our vast Knowledge Platforms unearthing new connections to be found and novel hypotheses to be generated.
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Elucidating the role of CREBBP co-activator in erythroid differentiation by literature mining and analysis
Posters presented at 18th International Conference on Genome Informatics (GIW 2007), Singapore Posters presented at RECOMB 2008 Singapore Posters presented at the 3rd International Biocuration Conference. 2009. Berlin, Germany
Differentiation of pluripotent hematopoietic stem cells into mature circulating erythrocytes are coordinated by a set of lineage- and tissue specific transcription factors. The two highly related nuclear proteins CREB binding protein (CBP or CREBBP) and p300 are co-activators that possess histone acetyltransferase activity, play a central role in the integration of transcription signals involving diverse cellular processes and differentiation pathways such as hematopoiesis, embryogenesis and so .We have been using literature mining successfully to unravel various biological processes and provide a concise view of regulation of the physiological networks. An interaction database NetPro™ was used as a source of all interactions in this study. By further network analysis, CBP is shown as a molecular integrator of hematopoietic differentiation. Several transcription factor nodes through which the master regulatory cofactor CBP binds and modulates the expression or activity of downstream genes involved in erythrocyte differentiation have been elucidated.
Community Standards in database
Uniform standard for capturing gene/protein names for family proteins and complex proteins with more than one subunit for functional activity is not available at present. The article brings out the need for a common standard for denoting these proteins by the text mining community.
NetPro™ Based Analysis of Probable Interaction Networks Involved in Pathology of Alzheimer's Disease- Predicting Targets and Therapeutic Agents
The study was aimed at using the protein interactions data from NetPro™ to understand the significance of differential regulation of genes in AD, as reported from a microarray study and to hypothesize possible molecular network(s) that might lead to the manifestation of the disease condition and predict probable targets or molecules of therapeutic significance. Interactions were also analyzed to find upstream node(s) that lead to the altered expression profile observed in Alzheimer's disease patients. The study highlighted the involvement of certain molecules like TNF, BDNF, PPARG etc and also calcium homeostatis as major nodes in the proposed interaction network for the Alzheimer disease pathogenesis. Certain small molecules that could have potential therapeutic significance have also been suggested from this study.
Role of interaction databases in studying cross talks between pathaways
Bio-molecular interaction database constitute a major source of data for understanding signaling pathways or in the course of drug discovery and other biologically relevant studies. NetPro™ is a bi molecular interaction database containing protein-protein, protein-small molecule and small molecule-small molecule interactions. Cross talks between pathways form an important link in understanding interactions in the physiological context. This analysis highlights the utility of interaction databases in understanding cross - talk between pathways.
Exploring protein protein interaction at domain level
There is always a need to validate the detected protein-protein interactions obtained by various high-through put experiments. Vast amount of data is available on protein interactions, domain information of a protein and interacting-domains without protein in context. Given that protein-protein interactions involve physical interactions between protein domains, domain-domain interaction information can be useful for validating, annotating, and even predicting protein interactions. With successful integration of interaction data points from NetPro™ with the public domain databases such as Pfam, Interdom and PROSITE, the domain level interaction of the vast repository of multidomain proteins and protein complexes can be deciphered and visualized.
Disease Target Screening and Evaluation with RNAi Data
In the drug discovery industry, RNA interference (RNAi) screens are popular for drug target identification and validation. Recently RNAi therapy has become the most promising hope for the treatment of many diseases. We propose a simple method of target screening and validation based on literature evidence, which may form the basis of extensive target identification studies. The approach is based on querying data from NetPro™ interaction database and NetPro™ Disease module using a customized JAVA based querying tool. The query tool is designed to provide an accessible method for screening of disease target genes, and to understand potential mechanisms of involvement of the identified targets to disease, validated by RNAi experimental data.
Ubiquitin-proteasome Pathway Genes and Prostate Cancer
Ubiquitin-proteasome system plays a significant role in pathogenesis, particularly in cancer. Understanding degradation of proteins through this pathway is important in short listing targets and drug design. Here proteasome regulated genes in general and specifically those involved in prostate cancer are analyzed using NetPro™, a hand curated interactome knowledgebase. The analysis brings out the utility of the database to understand molecular interactions and also importance of ubiquitin-proteasome pathway in cancer.
Analyzing the role of CREBP co-activator in erythroid differentiation-A literature mining approach
Differentiation of pluripotent hematopoietic stem cells into mature circulating erythrocytes are coordinated by a set of transcription factors that are lineage and tissue specifically restricted to the hematopoietic system. The two highly related nuclear proteins CREB binding protein (CBP or CREBBP) and p300 are co-activators that possess histone acetyltransferase activity and play a central role in the integration of transcription signals involving diverse cellular processes and differentiation pathways that include hematopoiesis. Using data from literature mining, we have shown CBP as a transcriptional regulator of hematopoietic cell differentiation with particular emphasis on the erythroid differentiation pathway.
Contrast Interaction database-A novel approach to study contextual relevance to interaction
Molecular interactions constitute the basis for all physiological processes in a cell. Till recent times, the major afflict faced by the scientific community was the inability to use information about molecular interactions dispersed in scientific literature. The birth of interaction databases catered data in a structured format, which became an essential and easily searchable resource for biologists. Having an easily searchable repository in hand, the scientific communities are now looking for more granular information to validate the data more precisely. In an effort to understand the needs of the scientific community we closely studied the details of molecular interactions. A very common revelation was that all interactions are tightly regulated by certain conditions or factors. The nature of interaction between two interacting molecules varies based on various factors, so much so that we found interesting instances of contrasting interactions between pair of molecules every now and then. Making a conscious effort, we built a pioneering database, NetPro™ Contrast Interactions database' based on this concept to bring such information at the disposal of the scientific community which otherwise would not have been easy to retrieve.
This study is made to bring contrast interactions into focus and state the importance of capturing such granular information by correlating with biologically relevant instances.
ONTOLOGY OF CELLS AND CELL LINES
Many ontologies have been developed since introduction of GO terms for gene annotation as can be seen from OLS (Ontology lookup service). Experimentally derived cell-lines are a major tool for biology research today. In spite of availability of the details on the cell-lines from American Type Cell Collection (ATCC) or European Collection of Cell Cultures (ECACC), the tissue type from which the cell-lines are developed are not easily integratable in biological databases. Cell lines are a major source of experimental model in biological research. If one were to pull out all interactions that arise from a specific organ, for example, it will be helpful if data from all the cell lines that are derived from that organ can be obtained from the database. With this aim, we developed hierarchical tree of cells/cell-lines present in our interaction database NetPro™. The cell-lines and other primary cells were placed in a hierarchical tree starting from organs. The parent and child terms are connected to each other by is_a and derived_from relationships. Preferred terms were taken from MeSH. Description notes and aliases were added to each cell-line. Cells are categorized as normal or pathological tissue derived experimental cells. It was developed in OBO format. About 2000 cell-lines are added in the ontology. The ontology tree helps in recruiting data relevant to specific tissues. For eg., if one were to analyze microarray data coming from prostate cancer tissue, it will be relevant to overlay the microarray data on interaction network experimentally shown to happen in prostate derived cells. The analyst only needs to pull out interaction reported in 'Prostate tissue'.
