scholarly journals Connectivity Problems on Heterogeneous Graphs

2018 ◽  
Author(s):  
Jimmy Wu ◽  
Alex Khodaverdian ◽  
Benjamin Weitz ◽  
Nir Yosef
Keyword(s):  
Computational Biology ◽  
Biological Networks ◽  
Single Cells ◽  
Network Connectivity ◽  
Interaction Network ◽  
Reference Database ◽  
Worst Case ◽  
Network Problem ◽  
Prize Collecting ◽  
Reference Graph

AbstractBackgroundNetwork connectivity problems are abundant in computational biology research, where graphs are used to represent a range of phenomena: from physical interactions between molecules to more abstract relationships such as gene co-expression. One common challenge in studying biological networks is the need to extract meaningful, small subgraphs out of large databases of potential interactions. A useful abstraction for this task turned out to be the Steiner network problems: given a reference “database” graph, find a parsimonious subgraph that satisfies a given set of connectivity demands. While this formulation proved useful in a number of instances, the next challenge is to account for the fact that the reference graph may not be static. This can happen for instance, when studying protein measurements in single cells or at different time points, whereby different subsets of conditions can have different protein milieu.Results and DiscussionWe introduce the condition Steiner network problem in which we concomitantly consider a set of distinct biological conditions. Each condition is associated with a set of connectivity demands, as well as a set of edges that are assumed to be present in that condition. The goal of this problem is to find a minimal subgraph that satisfies all the demands through paths that are present in the respective condition. We show that introducing multiple conditions as an additional factor makes this problem much harder to approximate. Specifically, we prove that for C conditions, this new problem is NP-hard to approximate to a factor of C – ϵ, for every C ≥ 2 and ϵ > 0, and that this bound is tight. Moving beyond the worst case, we explore a special set of instances where the reference graph grows monotonically between conditions, and show that this problem admits substantially improved approximation algorithms. We also developed an integer linear programming solver for the general problem and demonstrate its ability to reach optimality with instances from the human protein interaction network.ConclusionOur results demonstrate that in contrast to most connectivity problems studied in computational biology, accounting for multiplicity of biological conditions adds considerable complexity, which we propose to address with a new solver. Importantly, our results extend to several network connectivity problems that are commonly used in computational biology, such as Prize-Collecting Steiner Tree, and provide insight into the theoretical guarantees for their applications in a multiple condition setting.AvailabilityOur solver for the general condition Steiner network problem is available at https://github.com/YosefLab/condition_connectivity_problems

scholarly journals An Effective Statistical Integrative Algorithm (Aeiapp) for Protein Prediction

2019 ◽  
Vol 8 (11) ◽  
pp. 132-137 ◽  
Keyword(s):  
Protein Interaction ◽  
Biological Networks ◽  
Protein Interaction Network ◽  
Protein Identification ◽  
Research Work ◽  
Interaction Network ◽  
Integrative Approach ◽  
Target Proteins ◽  
Protein Protein Interaction ◽  
Protein Protein Interaction Network

The task of predicting target proteins for new drug discovery is typically difficult. Target proteins are biologically most important to control a keen functional process. The recent research of experimental and computational -based approaches has been widely used to predict target proteins using biological networks analysis techniques. Perhaps with available methods and statistical algorithm needs to be modified and should be clearer to tag the main target. Meanwhile identifying wrong protein leads to unwanted molecular interaction and pharmacological activity. In this research work, a novel method to identify essential target proteins using integrative graph coloring algorithm has been proposed. The proposed integrative approach helps to extract essential proteins in protein-protein interaction network (PPI) by analyzing neighborhood of the active target protein. Experimental results reviewed based on protein-protein interaction network for homosapiens showed that AEIAPP based approach shows an improvement in the essential protein identification by assuming the source protein as biologically proven protein. The AEIAPP statistical model has been compared with other state of art approaches on human PPI for various diseases to produce good accurate outcome in faster manner with little memory consumption.

scholarly journals Evaluation of the role of kras gene in colon cancer pathway using string and Cytoscape software

2020 ◽  
Vol 7 (6) ◽  
pp. 3835-3842
Author(s):  
Sandya Menon Prabhakaran Menon ◽  
Asita Elengoe
Keyword(s):  
Colon Cancer ◽  
Biological Networks ◽  
Screening Program ◽  
Interaction Network ◽  
Protein Network ◽  
Vegf Receptor ◽  
Protein Activity ◽  
Kras Gene ◽  
Network Interaction ◽  
Common Cancer

Introduction: cancer is one of the top three most commonly occurring cancer worldwide with more than 1.8 million cases in 2018. In Malaysia, cancer is the most common cancer in males and the second most common cancer in females. Albeit being the second most common form of cancer in Malaysia, there is a lack of informal or structured national cancer screening program in Malaysia and it remains a low priority in healthcare planning and expenditure. The risk of developing colon cancer is greatly influenced by factors such as lifestyle habits, genetic inheritance, diet, weight, and exercise. KRAS, the most frequently mutated oncogene in cancer, occurs in about 50 percent of cancers. This study maps the KRAS gene involved in colon cancer pathway using applications such as STRING version 11.0 and version 3.7.0 to provide a clear visualization of all the related and involved proteins and genes that interact with KRAS gene in the pathway. Methods: Using KRAS as a seed, a protein-protein interaction network was constructed with 3391 interactions which were retrieved from the STRING version 11.0 database. The protein network interaction was further grouped into 6 clusters using the MCODE application. Molecular function and biological processes of the genes involved in the KRAS protein network were determined using Biological Networks Gene Ontology (BiNGO). Results: According to the resulting protein-protein network interaction map, it revealed that KRAS mechanism and co-expressed genes interconnected with protein or enzyme binding, receptor signaling protein activity and vascular endothelial growth factor (VEGF) receptor 2 binding. Conclusion: Understanding these protein-protein interactions provide insight into cellular activities and thus aid in the understanding of the cause of disease.  

scholarly journals Community Detection in Large-Scale Bipartite Biological Networks

2021 ◽  
Vol 12 ◽  
Author(s):  
Genís Calderer ◽  
Marieke L. Kuijjer
Keyword(s):  
Biological Networks ◽  
Large Scale ◽  
Interaction Network ◽  
Gene Interaction ◽  
Community Structures ◽  
Gene Interaction Network ◽  
Structure Detection ◽  
Wide Range ◽  
Disease Associations ◽  
Or Gene

Networks are useful tools to represent and analyze interactions on a large, or genome-wide scale and have therefore been widely used in biology. Many biological networks—such as those that represent regulatory interactions, drug-gene, or gene-disease associations—are of a bipartite nature, meaning they consist of two different types of nodes, with connections only forming between the different node sets. Analysis of such networks requires methodologies that are specifically designed to handle their bipartite nature. Community structure detection is a method used to identify clusters of nodes in a network. This approach is especially helpful in large-scale biological network analysis, as it can find structure in networks that often resemble a “hairball” of interactions in visualizations. Often, the communities identified in biological networks are enriched for specific biological processes and thus allow one to assign drugs, regulatory molecules, or diseases to such processes. In addition, comparison of community structures between different biological conditions can help to identify how network rewiring may lead to tissue development or disease, for example. In this mini review, we give a theoretical basis of different methods that can be applied to detect communities in bipartite biological networks. We introduce and discuss different scores that can be used to assess the quality of these community structures. We then apply a wide range of methods to a drug-gene interaction network to highlight the strengths and weaknesses of these methods in their application to large-scale, bipartite biological networks.

A Transfer Learning Approach and Selective Integration of Multiple Types of Assays for Biological Network Inference

2013 ◽  
pp. 188-202
Author(s):  
Tsuyoshi Kato ◽  
Kinya Okada ◽  
Hisashi Kashima ◽  
Masashi Sugiyama
Keyword(s):  
Metabolic Network ◽  
Transfer Learning ◽  
Protein Interaction ◽  
Biological Networks ◽  
Protein Interaction Network ◽  
Network Inference ◽  
Interaction Network ◽  
Statistical Test ◽  
Learning Approach ◽  
Selective Integration

The authors’ algorithm was favorably examined on two kinds of biological networks: a metabolic network and a protein interaction network. A statistical test confirmed that the weight that our algorithm assigned to each assay was meaningful.

New Trends in Graph Mining

2010 ◽  
Vol 1 (1) ◽  
pp. 81-99 ◽  
Author(s):  
Francesco Bruno ◽  
Luigi Palopoli ◽  
Simona E. Rombo
Keyword(s):  
Computational Biology ◽  
Biological Networks ◽  
Graph Mining ◽  
Building Blocks ◽  
Biological Data ◽  
Future Research ◽  
Motif Extraction

Searching for repeated features characterizing biological data is fundamental in computational biology. When biological networks are under analysis, the presence of repeated modules across the same network (or several distinct ones) is shown to be very relevant. Indeed, several studies prove that biological networks can be often understood in terms of coalitions of basic repeated building blocks, often referred to as network motifs.This work provides a review of the main techniques proposed for motif extraction from biological networks. In particular, main intrinsic difficulties related to the problem are pointed out, along with solutions proposed in the literature to overcome them. Open challenges and directions for future research are finally discussed.

scholarly journals Combined Heuristic Attack Strategy on Complex Networks

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Marek Šimon ◽  
Iveta Dirgová Luptáková ◽  
Ladislav Huraj ◽  
Marián Hosťovecký ◽  
Jiří Pospíchal
Keyword(s):  
Complex Networks ◽  
Complex Network ◽  
Biological Networks ◽  
Case Scenario ◽  
Worst Case ◽  
Scale Free ◽  
Power Law Exponent ◽  
Spreading Disease ◽  
Heuristic Criterion ◽  
Attack Strategy

Usually, the existence of a complex network is considered an advantage feature and efforts are made to increase its robustness against an attack. However, there exist also harmful and/or malicious networks, from social ones like spreading hoax, corruption, phishing, extremist ideology, and terrorist support up to computer networks spreading computer viruses or DDoS attack software or even biological networks of carriers or transport centers spreading disease among the population. New attack strategy can be therefore used against malicious networks, as well as in a worst-case scenario test for robustness of a useful network. A common measure of robustness of networks is their disintegration level after removal of a fraction of nodes. This robustness can be calculated as a ratio of the number of nodes of the greatest remaining network component against the number of nodes in the original network. Our paper presents a combination of heuristics optimized for an attack on a complex network to achieve its greatest disintegration. Nodes are deleted sequentially based on a heuristic criterion. Efficiency of classical attack approaches is compared to the proposed approach on Barabási-Albert, scale-free with tunable power-law exponent, and Erdős-Rényi models of complex networks and on real-world networks. Our attack strategy results in a faster disintegration, which is counterbalanced by its slightly increased computational demands.

scholarly journals Analysing brain networks in population neuroscience: a case for the Bayesian philosophy

2020 ◽  
Vol 375 (1796) ◽  
pp. 20190661 ◽  
Author(s):  
Danilo Bzdok ◽  
Dorothea L. Floris ◽  
Andre F. Marquand
Keyword(s):  
Biological Networks ◽  
Network Connectivity ◽  
Autism Spectrum ◽  
Single Subject ◽  
Model Parameters ◽  
Philosophical Foundations ◽  
Probability Estimates ◽  
Rich Information ◽  
Epistemological Uncertainty ◽  
Coupling Phenomena

Network connectivity fingerprints are among today's best choices to obtain a faithful sampling of an individual's brain and cognition. Widely available MRI scanners can provide rich information tapping into network recruitment and reconfiguration that now scales to hundreds and thousands of humans. Here, we contemplate the advantages of analysing such connectome profiles using Bayesian strategies. These analysis techniques afford full probability estimates of the studied network coupling phenomena, provide analytical machinery to separate epistemological uncertainty and biological variability in a coherent manner, usher us towards avenues to go beyond binary statements on existence versus non-existence of an effect, and afford credibility estimates around all model parameters at play which thus enable single-subject predictions with rigorous uncertainty intervals. We illustrate the brittle boundary between healthy and diseased brain circuits by autism spectrum disorder as a recurring theme where, we argue, network-based approaches in neuroscience will require careful probabilistic answers. This article is part of the theme issue ‘Unifying the essential concepts of biological networks: biological insights and philosophical foundations’.

scholarly journals Robustness and lethality in multilayer biological molecular networks

2019 ◽  
Author(s):  
Xueming Liu ◽  
Enrico Maiorino ◽  
Arda Halu ◽  
Joseph Loscalzo ◽  
Jianxi Gao ◽  
...  
Keyword(s):  
Biological Networks ◽  
Regulatory Networks ◽  
Metabolic Diseases ◽  
Biological Systems ◽  
Interaction Network ◽  
Network Models ◽  
Global Network ◽  
Molecular Networks ◽  
Cancer Genes ◽  
Gene Regulatory

AbstractRobustness is a prominent feature of most biological systems. In a cell, the structure of the interactions between genes, proteins, and metabolites has a crucial role in maintaining the cell’s functionality and viability in presence of external perturbations and noise. Despite advances in characterizing the robustness of biological systems, most of the current efforts have been focused on studying homogeneous molecular networks in isolation, such as protein-protein or gene regulatory networks, neglecting the interactions among different molecular substrates. Here we propose a comprehensive framework for understanding how the interactions between genes, proteins and metabolites contribute to the determinants of robustness in a heterogeneous biological network. We integrate heterogeneous sources of data to construct a multilayer interaction network composed of a gene regulatory layer, and protein-protein interaction layer and a metabolic layer. We design a simulated perturbation process to characterize the contribution of each gene to the overall system’s robustness, defined as its influence over the global network. We find that highly influential genes are enriched in essential and cancer genes, confirming the central role of these genes in critical cellular processes. Further, we determine that the metabolic layer is more vulnerable to perturbations involving genes associated to metabolic diseases. By comparing the robustness of the network to multiple randomized network models, we find that the real network is comparably or more robust than expected in the random realizations. Finally, we analytically derive the expected robustness of multilayer biological networks starting from the degree distributions within or between layers. These results provide new insights into the non-trivial dynamics occurring in the cell after a genetic perturbation is applied, confirming the importance of including the coupling between different layers of interaction in models of complex biological systems.

scholarly journals Hub Genes Related to the Pathogenesis and Progression of Colorectal Cancer and Adenoma by Integrative Bioinformatics Approaches

2021 ◽  
Author(s):  
Yuxuan HUANG ◽  
Ge CUI
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Differentially Expressed Genes ◽  
Protein Interaction ◽  
Biological Networks ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Venn Diagram ◽  
Hub Genes ◽  
Protein Protein Interaction

Abstract Aims: To utilize the bioinformatics to analyze the differentially expressed genes (DEGs), interaction proteins, perform gene enrichment analysis, protein-protein interaction network (PPI) and map the hub genes between colorectal cancer(CRC) and colorectal adenocarcinomas(CA).Methods: We analyzed a microarray dataset (GSE32323 and GSE4183) from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in tumor tissues and non-cancerous tissues were identified using the dplyr and Venn diagram packages of the R Studio software. Functional annotation of the DEGs was performed using the Gene Ontology (GO) website. Pathway enrichment (KEGG) used the WebGestalt to analyze the data and R Studio to generate the graph. We constructed a protein–protein interaction (PPI) network of DEGs using STRING and Cytoscape software was used for visualization. Survival analysis of the hub genes and was performed using the online platform GEPIA to determine the prognostic value of the expression of hub genes in cell lines from CRC patients. The expression of molecules with prognostic values was validated on the UALCAN database. The expression of hub genes was examined using the Human Protein Atlas. Results: Applying the GEO2R analysis and R studio, we identified a total of 471 upregulated and 278 downregulated DEGs. By using the online database WebGestalt, we identified the most relevant biological networks involving DEGs with statistically significant differences in expression were mainly associated with biological processes involved in the cell proliferation, cell cycle transition, cell homeostasis and indicated the role of each DEGs in cell cycle regulation pathways. We found 10 hub genes with prognostic values were overexpressed in the CRC and CA samples.Conclusion: we found out ten hub genes and three core genes closely associated with the pathogenesis and prognosis of CRC and CA, which is of great significance for colorectal tumor early detection and prognosis evaluation.

scholarly journals From Protein Variations to Biological Processes and Pathways with NET-GE

2017 ◽  
Vol 3 (3) ◽  
pp. 45 ◽  
Author(s):  
Samuele Bovo ◽  
Pietro Di Lena ◽  
Pier Luigi Martelli ◽  
Piero Fariselli ◽  
Rita Casadio
Keyword(s):  
Biological Networks ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Biological Processes ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Hyperactivity Disorder ◽  
Gene Enrichment Analysis ◽  
Gene Enrichment ◽  
Common Technique

Gene enrichment analysis is a common technique for highlighting molecular pathways and biological processes of a phenotype. Such technique has recently evolved exploiting the information contained in biological networks. We developed NET-GE, a web server for network-based gene enrichment analyses. NET-GE defines functional associations between a list of genes/proteins and biological processes or pathways by identifying function-specific modules in a molecular interaction network. The peculiarity of NET-GE is the possibility to enrich terms not detectable by standard enrichment procedure. Here, we highlight with two specific applications the performances of NET-GE by computing which functional phenotypes can be associated with two different sets of genes related to Attention Deficit Hyperactivity Disorder and to an Obsessive-compulsive disorder, respectively.

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