Abstract
The ever-increasing capacity of biological molecular data acquisition outpaces our ability to understand the meaningful relationships between molecules in a cell. Multiple databases were developed to store and organize these molecular data. However, emerging fundamental questions about concerted functions of these molecules in hierarchical cellular networks are poorly addressed. Here we review recent advances in the development of publically available databases that help us analyze the signal integration and processing by multilayered networks that specify biological responses in model organisms and human cells
Highlights
Eukaryotic cells respond to a myriad of external and internal cues via a multilayered signaling network
At the top layer of this network, there are plasma membrane receptors which sense changes in the surrounding environment and play important roles in the communication between cells and tissues. These receptors trigger multiple interweaved signaling pathways which operate via protein-protein interactions (PPI) and posttranslational protein modifications (PTMs), such as phosphorylation and ubiquitination, to generate specific biological responses
The production, degradation, and translation of messenger RNAs (mRNAs) is delicately regulated by a network of non-coding RNAs, which include micro RNAs and small inhibitory RNAs
Summary
Rapid advances in modern -omics techniques, our ability to acquire vast amounts of biological data increasingly exceeds our ability to interpret these data. IntAct, STRING, HPRD, BioGRID, WI8, DroID, YEASTRACT, and SGD [2,3,4,5,6,7,8,9] store curated information about protein interactions; PHOSIDA, PhosphoSitePlus, PhosphoELM, NetPhosK, NetworKIN, PREDIKIN, and Scansite [10,11,12,13,14,15] accumulate knowledge about protein phosphorylation and increasingly about other PTMs; EdgeDB, REDfly, JASPAR, ENCODE, PAZAR, ABS, ORegAnno, and others [16,17,18,19,20,21,22] provide information about transcriptional regulatory interactions; miRBase, PutMir, Miranda, TargetScan, and miRecords [23,24,25,26,27] contain information on miRNAs and mRNA targets of miRNAs; and PutMir, TransmiR, and ENCODE [19,25,28] supply information about TFs regulating miRNA expressions Many of these databases are highly comprehensive in their specialized areas, yet they do not provide an integrated picture of how multiple layers of biological regulation (PPI, PTM, TF-DNA interactions, and transcriptional and translational feedbacks) cooperate to enable the signal integration and processing that determine cellular responses. Many components of these pathways control transcriptions and translation, thereby initiating new layers of molecular interactions
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