Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Using Multilayer Heterogeneous Networks to Infer Functions of Phosphorylated Sites.

ABSTRACT: Mass spectrometry-based quantitative phosphoproteomics has become an essential approach in the study of cellular processes such as signaling. Commonly used methods to analyze phosphoproteomics datasets depend on generic, gene-centric annotations such as Gene Ontology terms, which do not account for the function of a protein in a particular phosphorylation state. Analysis of phosphoproteomics data is hampered by a lack of phosphorylated site-specific annotations. We propose a method that combines shotgun phosphoproteomics data, protein-protein interactions, and functional annotations into a heterogeneous multilayer network. Phosphorylation sites are associated to potential functions using a random walk on the heterogeneous network (RWHN) algorithm. We validated our approach against a model of the MAPK/ERK pathway and functional annotations from PhosphoSitePlus and were able to associate differentially regulated sites on the same proteins to their previously described specific functions. We further tested the algorithm on three previously published datasets and were able to reproduce their experimentally validated conclusions and to associate phosphorylation sites with known functions based on their regulatory patterns. Our approach provides a refinement of commonly used analysis methods and accurately predicts context-specific functions for sites with similar phosphorylation profiles.

SUBMITTER: Watson J

PROVIDER: S-EPMC8256419 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Using null models to infer microbial co-occurrence networks.

Project description:Although microbial communities are ubiquitous in nature, relatively little is known about the structural and functional roles of their constituent organisms' underlying interactions. A common approach to study such questions begins with extracting a network of statistically significant pairwise co-occurrences from a matrix of observed operational taxonomic unit (OTU) abundances across sites. The structure of this network is assumed to encode information about ecological interactions and processes, resistance to perturbation, and the identity of keystone species. However, common methods for identifying these pairwise interactions can contaminate the network with spurious patterns that obscure true ecological signals. Here, we describe this problem in detail and develop a solution that incorporates null models to distinguish ecological signals from statistical noise. We apply these methods to the initial OTU abundance matrix and to the extracted network. We demonstrate this approach by applying it to a large soil microbiome data set and show that many previously reported patterns for these data are statistical artifacts. In contrast, we find the frequency of three-way interactions among microbial OTUs to be highly statistically significant. These results demonstrate the importance of using appropriate null models when studying observational microbiome data, and suggest that extracting and characterizing three-way interactions among OTUs is a promising direction for unraveling the structure and function of microbial ecosystems.

| S-EPMC5426617 | biostudies-literature

Biased Random Walk With Restart on Multilayer Heterogeneous Networks for MiRNA-Disease Association Prediction.

Project description:Numerous experiments have proved that microRNAs (miRNAs) could be used as diagnostic biomarkers for many complex diseases. Thus, it is conceivable that predicting the unobserved associations between miRNAs and diseases is extremely significant for the medical field. Here, based on heterogeneous networks built on the information of known miRNA-disease associations, miRNA function similarity, disease semantic similarity, and Gaussian interaction profile kernel similarity for miRNAs and diseases, we developed a computing model of biased random walk with restart on multilayer heterogeneous networks for miRNA-disease association prediction (BRWRMHMDA) through enforcing degree-based biased random walk with restart (BRWR). Assessment results reflected that an AUC of 0.8310 was gained in local leave-one-out cross-validation (LOOCV), which proved the calculation algorithm's good performance. Besides, we carried out BRWRMHMDA to prioritize candidate miRNAs for esophageal neoplasms based on HMDD v2.0. We further prioritize candidate miRNAs for breast neoplasms based on HMDD v1.0. The local LOOCV results and performance analysis of the case study all showed that the proposed model has good and stable performance.

| S-EPMC8384471 | biostudies-literature

Efficient community detection in multilayer networks using boolean compositions.

Project description:Networks (or graphs) are used to model the dyadic relations between entities in complex systems. Analyzing the properties of the networks reveal important characteristics of the underlying system. However, in many disciplines, including social sciences, bioinformatics, and technological systems, multiple relations exist between entities. In such cases, a simple graph is not sufficient to model these multiple relations, and a multilayer network is a more appropriate model. In this paper, we explore community detection in multilayer networks. Specifically, we propose a novel network decoupling strategy for efficiently combining the communities in the different layers using the Boolean primitives AND, OR, and NOT. Our proposed method, network decoupling, is based on analyzing the communities in each network layer individually and then aggregating the analysis results. We (i) describe our network decoupling algorithms for finding communities, (ii) present how network decoupling can be used to express different types of communities in multilayer networks, and (iii) demonstrate the effectiveness of using network decoupling for detecting communities in real-world and synthetic data sets. Compared to other algorithms for detecting communities in multilayer networks, our proposed network decoupling method requires significantly lower computation time while producing results of high accuracy. Based on these results, we anticipate that our proposed network decoupling technique will enable a more detailed analysis of multilayer networks in an efficient manner.

| S-EPMC10481956 | biostudies-literature

Using dynamic noise propagation to infer causal regulatory relationships in biochemical networks.

Project description:Cellular decision making is accomplished by complex networks, the structure of which has traditionally been inferred from mean gene expression data. In addition to mean data, quantitative measures of distributions across a population can be obtained using techniques such as flow cytometry that measure expression in single cells. The resulting distributions, which reflect a population's variability or noise, constitute a potentially rich source of information for network reconstruction. A significant portion of molecular noise in a biological process is propagated from the upstream regulators. This propagated component provides additional information about causal network connections. Here, we devise a procedure in which we exploit equations for dynamic noise propagation in a network under nonsteady state conditions to distinguish between alternate gene regulatory relationships. We test our approach in silico using data obtained from stochastic simulations as well as in vivo using experimental data collected from synthetic circuits constructed in yeast.

| S-EPMC4384829 | biostudies-other

Engineering multilayer chemical networks.

Project description:Dynamic multilevel systems emerged in the last few years as new platforms to study thermodynamic systems. In this work, unprecedented fully communicated three-level systems are studied. First, different conditions were screened to selectively activate thiol/dithioacetal, thiol/thioester, and thiol/disulfide exchanges, individually or in pairs. Some of those conditions were applied, sequentially, to build multilayer dynamic systems wherein information, in the form of relative amounts of building blocks, can be directionally transmitted between different exchange pools. As far as we know, this is the first report of one synthetic dynamic chemical system where relationships between layers can be changed through network operations.

| S-EPMC6844274 | biostudies-literature

Control of Multilayer Networks.

Project description:The controllability of a network is a theoretical problem of relevance in a variety of contexts ranging from financial markets to the brain. Until now, network controllability has been characterized only on isolated networks, while the vast majority of complex systems are formed by multilayer networks. Here we build a theoretical framework for the linear controllability of multilayer networks by mapping the problem into a combinatorial matching problem. We found that correlating the external signals in the different layers can significantly reduce the multiplex network robustness to node removal, as it can be seen in conjunction with a hybrid phase transition occurring in interacting Poisson networks. Moreover we observe that multilayer networks can stabilize the fully controllable multiplex network configuration that can be stable also when the full controllability of the single network is not stable.

| S-EPMC4751610 | biostudies-literature

Using empirical biological knowledge to infer regulatory networks from multi-omics data.

Project description:BackgroundIntegration of multi-omics data can provide a more complex view of the biological system consisting of different interconnected molecular components, the crucial aspect for developing novel personalised therapeutic strategies for complex diseases. Various tools have been developed to integrate multi-omics data. However, an efficient multi-omics framework for regulatory network inference at the genome level that incorporates prior knowledge is still to emerge.ResultsWe present IntOMICS, an efficient integrative framework based on Bayesian networks. IntOMICS systematically analyses gene expression, DNA methylation, copy number variation and biological prior knowledge to infer regulatory networks. IntOMICS complements the missing biological prior knowledge by so-called empirical biological knowledge, estimated from the available experimental data. Regulatory networks derived from IntOMICS provide deeper insights into the complex flow of genetic information on top of the increasing accuracy trend compared to a published algorithm designed exclusively for gene expression data. The ability to capture relevant crosstalks between multi-omics modalities is verified using known associations in microsatellite stable/instable colon cancer samples. Additionally, IntOMICS performance is compared with two algorithms for multi-omics regulatory network inference that can also incorporate prior knowledge in the inference framework. IntOMICS is also applied to detect potential predictive biomarkers in microsatellite stable stage III colon cancer samples.ConclusionsWe provide IntOMICS, a framework for multi-omics data integration using a novel approach to biological knowledge discovery. IntOMICS is a powerful resource for exploratory systems biology and can provide valuable insights into the complex mechanisms of biological processes that have a vital role in personalised medicine.

| S-EPMC9396869 | biostudies-literature

An approach to infer putative disease-specific mechanisms using neighboring gene networks.

Project description:MotivationThe ultimate goal of any experiment is to understand the biological phenomena underlying the condition investigated. This process often results in genes network through which a certain biological mechanism is explained. Such networks have been proven to be extremely useful, for the prediction of mechanisms of action of drugs or the responses of an organism to a specific impact (e.g. a disease, a treatment, etc.). Here, we introduce an approach able to build a network that captures the putative mechanisms at play in the given condition, by using datasets from multiple experiments studying the same phenotype. This method takes advantage of known interactions extracted from multiple sources such as protein-protein interactions and curated biological pathways. Based on such prior knowledge, we overcome the drawbacks of snap-shot data by considering the possible effects of each gene on its neighbors.ResultsWe show the effectiveness of this approach in three different case studies and validate the results in two ways considering the identified genes and interactions between them. We compare our findings with the results of two widely-used methods in the same category as well as the classical approach of selecting differentially expressed (DE) genes in an investigated condition. The results show that 'neighbor-net' analysis is able to report biological mechanisms that are significantly relevant to the given diseases in all the three case studies, and performs better compared to all reference methods using both validation approaches.Availability and implementationThe proposed method is implemented as in R and will be available an a Bioconductor package.Supplementary informationSupplementary data are available at Bioinformatics online.

| S-EPMC5870849 | biostudies-literature

Improving prediction and assessment of global fires using multilayer neural networks.

Project description:Fires determine vegetation patterns, impact human societies, and are a part of complex feedbacks into the global climate system. Empirical and process-based models differ in their scale and mechanistic assumptions, giving divergent predictions of fire drivers and extent. Although humans have historically used and managed fires, the current role of anthropogenic drivers of fires remains less quantified. Whereas patterns in fire-climate interactions are consistent across the globe, fire-human-vegetation relationships vary strongly by region. Taking a data-driven approach, we use an artificial neural network to learn region-specific relationships between fire and its socio-environmental drivers across the globe. As a result, our models achieve higher predictability as compared to many state-of-the-art fire models, with global spatial correlation of 0.92, monthly temporal correlation of 0.76, interannual correlation of 0.69, and grid-cell level correlation of 0.60, between predicted and observed burned area. Given the current socio-anthropogenic conditions, Equatorial Asia, southern Africa, and Australia show a strong sensitivity of burned area to temperature whereas northern Africa shows a strong negative sensitivity. Overall, forests and shrublands show a stronger sensitivity of burned area to temperature compared to savannas, potentially weakening their status as carbon sinks under future climate-change scenarios.

| S-EPMC7870964 | biostudies-literature

Understanding cancer complexome using networks, spectral graph theory and multilayer framework.

Project description:Cancer complexome comprises a heterogeneous and multifactorial milieu that varies in cytology, physiology, signaling mechanisms and response to therapy. The combined framework of network theory and spectral graph theory along with the multilayer analysis provides a comprehensive approach to analyze the proteomic data of seven different cancers, namely, breast, oral, ovarian, cervical, lung, colon and prostate. Our analysis demonstrates that the protein-protein interaction networks of the normal and the cancerous tissues associated with the seven cancers have overall similar structural and spectral properties. However, few of these properties implicate unsystematic changes from the normal to the disease networks depicting difference in the interactions and highlighting changes in the complexity of different cancers. Importantly, analysis of common proteins of all the cancer networks reveals few proteins namely the sensors, which not only occupy significant position in all the layers but also have direct involvement in causing cancer. The prediction and analysis of miRNAs targeting these sensor proteins hint towards the possible role of these proteins in tumorigenesis. This novel approach helps in understanding cancer at the fundamental level and provides a clue to develop promising and nascent concept of single drug therapy for multiple diseases as well as personalized medicine.

| S-EPMC5290734 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data