Reconstructing Gene Networks Using Gene Expression Profiles

2010 ◽  
pp. 35-51
Author(s):  
Mario Lauria ◽  
Diego Bernardo
Keyword(s):  
Gene Expression ◽  
Gene Networks ◽  
Expression Profiles ◽  
Gene Expression Profiles

scholarly journals Analysis of blood-based gene expression in idiopathic Parkinson disease

Neurology ◽  
2017 ◽  
Vol 89 (16) ◽  
pp. 1676-1683 ◽  
Author(s):  
Ron Shamir ◽  
Christine Klein ◽  
David Amar ◽  
Eva-Juliane Vollstedt ◽  
Michael Bonin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson Disease ◽  
Gene Networks ◽  
Large Scale ◽  
Expression Profiles ◽  
Area Under The Curve ◽  
Gene Expression Profiles ◽  
Gene Signature ◽  
Gene Profiles ◽  
Independent Test

Objective:To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples).Methods:Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks.Results:A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was identified with the training cohort and successfully replicated in both an independent validation cohort (area under the curve [AUC] = 0.79, p = 7.13E–6) and a subsequent independent test cohort (AUC = 0.74, p = 4.2E–4). Network analysis of the signature revealed gene enrichment in pathways, including metabolism, oxidation, and ubiquitination/proteasomal activity, and misregulation of mitochondria-localized genes, including downregulation of COX4I1, ATP5A1, and VDAC3.Conclusions:We present a large-scale study of PD gene expression profiling. This work identifies a reliable blood-based PD signature and highlights the importance of large-scale patient cohorts in developing potential PD biomarkers.

Building Gene Networks by Analyzing Gene Expression Profiles

2019 ◽  
pp. 27-44
Author(s):  
Crescenzio Gallo
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Gene Networks ◽  
Dna Microarrays ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Expression Data ◽  
Gene Expressions ◽  
Over Time

The possible applications of modeling and simulation in the field of bioinformatics are very extensive, ranging from understanding basic metabolic paths to exploring genetic variability. Experimental results carried out with DNA microarrays allow researchers to measure expression levels for thousands of genes simultaneously, across different conditions and over time. A key step in the analysis of gene expression data is the detection of groups of genes that manifest similar expression patterns. In this chapter, the authors examine various methods for analyzing gene expression data, addressing the important topics of (1) selecting the most differentially expressed genes, (2) grouping them by means of their relationships, and (3) classifying samples based on gene expressions.

EFFECTIVE MODELS FOR GENE NETWORKS AND THEIR APPLICATIONS

2012 ◽  
Vol 07 (01n02) ◽  
pp. 41-70 ◽  
Author(s):  
JASON SHULMAN ◽  
LARS SEEMANN ◽  
GREGG W. ROMAN ◽  
GEMUNU H. GUNARATNE
Keyword(s):  
Gene Expression ◽  
Gene Networks ◽  
Gene Network ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Stationary Solutions ◽  
The State ◽  
Effective Model ◽  
Knockout Mutant ◽  
Double Knockout

Networks are used to abstract large, highly-coupled sets of objects. Their analyses have included network classification into a few broad classes and selection of small substructures that perform simple yet common tasks. One issue that has received little attention is how the state of a network can be moved according to a pre-specified set of guidelines. In this paper, we address this question in the context of gene networks. In general, neither the full membership of the gene network associated with a biological process nor the precise form of interactions between nodes is known. What is available, through microarrays or sequencing, are gene expression profiles of an organism or its viable mutants. Our approach relies only on these expression profiles, and not on the availability of an accurate model for the network. The first step is to select a small set of core- or master- nodes, such as transcription factors or microRNAs, that can be used to alter the levels of many of the remaining genes in the network. We ask how the state — or solution — of the gene network changes as the levels of these master nodes are altered externally. The object of our study is, not the network, but the surface of these solutions. We argue that it can be approximated using gene expression profiles of the organism and single manipulation of master node activity. This is done through an "effective model." The effective model as well as error estimates for its predictions can be derived from experimental data. The method is validated using synthetic gene networks that have stationary solutions and those that are periodically driven, e.g., circadian networks. An effective model for the oxygen-deprivation network of E.coli is constructed using previously published gene expression profiles, and used to predict the expression levels in a double knockout mutant. Less that 30% of the predictions lie outside the 5% confidence level. We propose the use of the effective model methodology to compute how Drosophila melanogaster in the normal state can be genetically altered into a pre-defined sleep deprived-like state.

scholarly journals Finding prognostic gene pairs for cancer from patient-specific gene networks

2019 ◽  
Vol 12 (S8) ◽  
Author(s):  
Byungkyu Park ◽  
Wook Lee ◽  
Inhee Park ◽  
Kyungsook Han
Keyword(s):  
Gene Expression ◽  
Gene Networks ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Patient Specific ◽  
Specific Gene ◽  
Gene Signatures ◽  
Gene Pairs ◽  
Prognostic Gene ◽  
Gene Correlation

Abstract Background Molecular characterization of individual cancer patients is important because cancer is a complex and heterogeneous disease with many possible genetic and environmental causes. Many studies have been conducted to identify diagnostic or prognostic gene signatures for cancer from gene expression profiles. However, some gene signatures may fail to serve as diagnostic or prognostic biomarkers and gene signatures may not be found in gene expression profiles. Methods In this study, we developed a general method for constructing patient-specific gene correlation networks and for identifying prognostic gene pairs from the networks. A patient-specific gene correlation network was constructed by comparing a reference gene correlation network from normal samples to a network perturbed by a single patient sample. The main difference of our method from previous ones includes (1) it is focused on finding prognostic gene pairs rather than prognostic genes and (2) it can identify prognostic gene pairs from gene expression profiles even when no significant prognostic genes exist. Results Evaluation of our method with extensive data sets of three cancer types (breast invasive carcinoma, colon adenocarcinoma, and lung adenocarcinoma) showed that our approach is general and that gene pairs can serve as more reliable prognostic signatures for cancer than genes. Conclusions Our study revealed that prognosis of individual cancer patients is associated with the existence of prognostic gene pairs in the patient-specific network and the size of a subnetwork of the prognostic gene pairs in the patient-specific network. Although preliminary, our approach will be useful for finding gene pairs to predict survival time of patients and to tailor treatments to individual characteristics. The program for dynamically constructing patient-specific gene networks and for finding prognostic gene pairs is available at http://bclab.inha.ac.kr/pancancer.

scholarly journals PhytoNet: Comparative co-expression network analyses across phytoplankton and land plants

2018 ◽  
Author(s):  
Camilla Ferrari ◽  
Sebastian Proost ◽  
Colin Ruprecht ◽  
Marek Mutwil
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Gene Networks ◽  
Photosynthetic Activity ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Land Plants ◽  
Expression Data ◽  
Network Analyses ◽  
Crucial Component

ABSTRACTPhytoplankton consists of autotrophic, photosynthesizing microorganisms that are a crucial component of freshwater and ocean ecosystems. However, despite being the major primary producers of organic compounds, accounting for half of the photosynthetic activity worldwide and serving as the entry point to the food chain, functions of most of the genes of the model phytoplankton organisms remain unknown. To remedy this, we have gathered publicly available expression data for one chlorophyte, one rhodophyte, one haptophyte, two heterokonts and four cyanobacteria and integrated it into our PlaNet (Plant Networks) database, which now allows mining gene expression profiles and identification of co-expressed genes of 19 species. We exemplify how the co-expressed gene networks can be used to reveal functionally related genes and how the comparative features of PhytoNet allow detection of conserved transcriptional programs between cyanobacteria, green algae, and land plants. Additionally, we illustrate how the database allows detection of duplicated transcriptional programs within an organism, as exemplified by two DNA repair programs within Chlamydomonas reinhardtii. PhytoNet is available from www.gene2function.de.

scholarly journals Tensor Decomposition of Stimulated Monocyte and Macrophage Gene Expression Profiles Identifies Neurodegenerative Disease-specific Trans-eQTLs

2018 ◽  
Author(s):  
Satesh Ramdhani ◽  
Elisa Navarro ◽  
Evan Udine ◽  
Brian M. Schilder ◽  
Madison Parks ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Variants ◽  
Gene Networks ◽  
Disease Risk ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Tensor Decomposition ◽  
Innate Immune ◽  
Primary Role ◽  
Expression Of Genes

AbstractRecent human genetic studies suggest that cells of the innate immune system have a primary role in the pathogenesis of neurodegenerative diseases. However, the results from these studies often do not elucidate how the genetic variants affect the biology of these cells to modulate disease risk. Here, we applied a tensor decomposition method to uncover disease-associated gene networks linked to distal genetic variation in stimulated human monocytes and macrophages gene expression profiles. We report robust evidence that some disease-associated genetic variants affect the expression of multiple genes in trans. These include a Parkinson’s disease locus influencing the expression of genes mediated by a protease that controls lysosomal function, and Alzheimer’s disease loci influencing the expression of genes involved in type 1 interferon signaling, myeloid phagocytosis, and complement cascade pathways. Overall, we uncover gene networks in induced innate immune cells linked to disease-associated genetic variants, which may help elucidate the underlying biology of disease.

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