Ariadne's ChemEffect and Pathway Studio knowledge base

Yuryev, Anton; Kotelnikova, Ekaterina; Daraselia, Nikolai

doi:10.1517/17460440903413488

Cited by 65 publications

(61 citation statements)

References 38 publications

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“…Subnetwork Enrichment Pathway Analyses and Statistical Testing-The Elsevier's Pathway Studio version 9.0 (Ariadne Genomics/ Elsevier) was used to deduce relationships among differentially expressed proteomics protein candidates using the Ariadne ResNetdatabase (25,26). "Subnetwork Enrichment Analysis" (SNEA) algorithm was selected to extract statistically significant altered biological and functional pathways pertaining to each identified set of protein hits (C1, C2, C3, R1, R2, and R3 sets).…”

mentioning

confidence: 99%

Proteomic Analysis of the Spatio-temporal Based Molecular Kinetics of Acute Spinal Cord Injury Identifies a Time- and Segment-specific Window for Effective Tissue Repair

Devaux¹,

Cizkova²,

Quanico³

et al. 2016

Molecular & Cellular Proteomics

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Spinal cord injury (SCI) represents a major debilitating health issue with a direct socioeconomic burden on the public and private sectors worldwide. Although several studies have been conducted to identify the molecular progression of injury sequel due from the lesion site, still the exact underlying mechanisms and pathways of injury development have not been fully elucidated. In this work, based on OMICs, 3D matrix-assisted laser desorption ionization (MALDI) imaging, cytokines arrays, confocal imaging we established for the first time that molecular and cellular processes occurring after SCI are altered between the lesion proximity, i.e. rostral and caudal segments nearby the lesion (R1-C1) whereas segments distant from R1-C1, i.e. R2-C2 and R3-C3 levels coexpressed factors implicated in neurogenesis. Delay in T regulators recruitment between R1 and C1 favor discrepancies between the two segments. This is also reinforced by presence of neurites outgrowth inhibitors in C1, absent in R1. Moreover

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mentioning

confidence: 99%

Proteomic Analysis of the Spatio-temporal Based Molecular Kinetics of Acute Spinal Cord Injury Identifies a Time- and Segment-specific Window for Effective Tissue Repair

Devaux¹,

Cizkova²,

Quanico³

et al. 2016

Molecular & Cellular Proteomics

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“…Algorithm performance heavily depends on Resnet [30], [59], [60], [61], global literature-derived network of over 1,500,000 relations which were extracted by automatic analysis of more than 22 million PubMed abstracts and 880,000 full-text articles. Many relations between entities stored in Resnet database are indirect (for example, expression links between non-transcription factors and downstream genes) and can be obtained only from literature-based analysis and not from experimental data.…”

Section: Discussionmentioning

confidence: 99%

Clustering Gene Expression Regulators: New Approach to Disease Subtyping

et al. 2014

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One of the main challenges in modern medicine is to stratify different patient groups in terms of underlying disease molecular mechanisms as to develop more personalized approach to therapy. Here we propose novel method for disease subtyping based on analysis of activated expression regulators on a sample-by-sample basis. Our approach relies on Sub-Network Enrichment Analysis algorithm (SNEA) which identifies gene subnetworks with significant concordant changes in expression between two conditions. Subnetwork consists of central regulator and downstream genes connected by relations extracted from global literature-extracted regulation database. Regulators found in each patient separately are clustered together and assigned activity scores which are used for final patients grouping. We show that our approach performs well compared to other related methods and at the same time provides researchers with complementary level of understanding of pathway-level biology behind a disease by identification of significant expression regulators. We have observed the reasonable grouping of neuromuscular disorders (triggered by structural damage vs triggered by unknown mechanisms), that was not revealed using standard expression profile clustering. For another experiment we were able to suggest the clusters of regulators, responsible for colorectal carcinoma vs adenoma discrimination and identify frequently genetically changed regulators that could be of specific importance for the individual characteristics of cancer development. Proposed approach can be regarded as biologically meaningful feature selection, reducing tens of thousands of genes down to dozens of clusters of regulators. Obtained clusters of regulators make possible to generate valuable biological hypotheses about molecular mechanisms related to a clinical outcome for individual patient.

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“…This software was used to interpret biological meaning from gene (protein) expression, build and analyze pathways, and find relationships among genes, proteins, cell processes, and diseases as indexed by the ResNet database (54, 55). “Subnetwork Enrichment Analysis” (SNEA) algorithm was selected to extract statistically significant altered biological and functional pathways pertaining to each identified set of protein hits in our study.…”

Section: Methodsmentioning

confidence: 99%

Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats

et al. 2016

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Traumatic brain injury (TBI) represents a critical health problem of which diagnosis, management, and treatment remain challenging. TBI is a contributing factor in approximately one-third of all injury-related deaths in the United States. The Centers for Disease Control and Prevention estimate that 1.7 million people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics–systems biology is proving to be a prominent tool in biomarker discovery for central nervous system injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI) model of experimental TBI in rat model to assess the temporal–global proteome changes after acute (1 day) and for the first time, subacute (7 days), post-injury time frame using the established cation–anion exchange chromatography-1D SDS gel electrophoresis LC–MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entity, we used in silico systems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1 day) and subacute (7 days) periods post-TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7 days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is among the first to assess temporal neuroproteome changes in the CCI model. Data presented here unveil potential neural biomarkers and therapeutic targets that could be used for diagnosis, for treatment and, most importantly, for temporal prognostic assessment following brain injury. Of interest, this work relies on in silico bioinformatics approach to draw its conclusion; further work is conducted for functional studies to validate and confirm the omics data obtained.

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Ariadne's ChemEffect and Pathway Studio knowledge base

Abstract: Integrated literature-derived protein and chemical knowledge bases can rationalize many aspects of drug development process including drug repositioning and biomarker design.

Cited by 65 publications

References 38 publications

Proteomic Analysis of the Spatio-temporal Based Molecular Kinetics of Acute Spinal Cord Injury Identifies a Time- and Segment-specific Window for Effective Tissue Repair

Proteomic Analysis of the Spatio-temporal Based Molecular Kinetics of Acute Spinal Cord Injury Identifies a Time- and Segment-specific Window for Effective Tissue Repair

Clustering Gene Expression Regulators: New Approach to Disease Subtyping

Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats

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