Virtual Interactomics of Proteins from Biochemical Standpoint

Table 4

Online accessible tools for PPI network assembly, reevaluation, and comparison.

	Purpose	Input	Evaluation results	Network content	Internet accessibility	References
Program tools
PINTA	Resource for the prioritization of disease related candidate genes based on the differential expression of their neighborhood in a genome-wide protein-protein interaction network.	Files with disease-specific expression data	Internal scores, 𝑃 values, Bonferroni–Holm 𝑃-values	menu: human, mouse, rat, worm; (C. elegans) and yeast P-PIN	http://www.esat.kuleuven.be/pinta/	[221]
PCFamily	Finds homologous structure complexes of the query using BLASTP to search the structural template database	QS or QS set in FASTA format	𝑍-value agreement ratio	941 protein complexes	http://pcfamily.life.nctu.edu.tw	[236]
BisoGenet	Build and visualize biological networks in a fast and user-friendly manner including P-PIN	List of identifiers	Node degrees, cluster coefficients	5365 human genes	http://bio.cigb.edu.cu/bisogenet-cytoscape/	[245]
DynaMod	Identifies significant functional modules reflecting the change of modularity and differential expressions that are correlated with gene expression profiles under different conditions	Genome-wide expression profile	𝑍-score, Bonferroni or FDR 𝑃-values	In frame of GSEA	http://biocondor6.kaist.ac.kr/dynamod/	[241]
TORQUE	Cross species querying allows users to run topology-free queries on predefined or user-provided target networks resulting in subnetwork of the target network most similar to query subset	Seq of compared sets, query list, target P-PIN	Thickness of the edge	5430 proteins, 39 936 interactions	http://www.cs.tau.ac.il/~bnet/torque.html	[246]
NetworkBLAST	Identifies protein complexes within and across species, forming html page with links to schemes of interactions within complexes and additional graph data files	Files with ^*PPI, BLPE ^*PPI	likelihood based density score	species related P-PIN; ^*two species; ^*single species	http://www.cs.tau.ac.il/~roded/networkblast.htm	[234]
Databases
STRING	A database of functional interaction networks of proteins, globally integrated and scored	Search based on gene annotations	probabilistic confidence score	>1100 completely sequenced organisms	http://string-db.org	[251]
ChemProt	Disease chemical biology database including 7×10^5 chemicals and two millions chemical-protein interactions; indicates a possible formation of disease-associated protein complexes	Compound and protein identifiers	compilation of multiple chemical-protein annotations	30 578 proteins; 2227 disease-related proteins, 428 429 PPI	http://www.cbs.dtu.dk/services/ChemProt/	[252]
NetAge	Database and network analysis tools for biogerontological research (integrity and functionality of P-PIN is under a tight epigenetic control)	Tools for searching and browsing	experimental evidence about interactions	miRNA-regulated P-PIN in age-related diseases	http://www.netage-project.org	[253]
BioGRID	All interactions in BioGRID are available through the Osprey visualization system, which can be used to query network organization in a user-defined fashion	Intuitive graphical interface	experimental evidence about interactions	Over 198 000 genetic + protein interactions from six species	http://www.thebiogrid.org	[254]
EHCO	Encyclopedia of Hepatocellular Carcinoma genes Online collect, organize and compare unsorted HCC-related studies	CMS	NL processing and softbots	97 proteins, 47 highly interactive, 18 hubs	http://ehco.iis.sinica.edu.tw	[255]
IntNetDB v1.0	A database providing automatic prediction and visualization of PPI network among genes of interest; analysis includes domain-domain interactions, known gene contexts, crossvalidation, and so forth	list of query gene identifiers	likelihood ratio following from Bayesian analysis	concerns 27 species contains GSP and GSN from HPRD	http://hanlab.genetics.ac.cn/IntNetDB.htm	[256]

^*Independent alternatives; BLPE: BLASTP 𝐸 values between pairs of proteins from each of the compared species; CMS: content management system; GSEA: gene set enrichment analyses; GSP, GSN: gold standard positive and a gold standard negative dataset of HPRD, respectively; HCC: hepatocellular carcinoma; HPRD: human protein reference database; NL: natural language; PE: probabilistic evaluation; PPI: protein-protein interactions; QS: query sequences; seq: sequences.