The Integration and Annotation of the Human Interactome in the UniHI Database

2011 ◽  
pp. 175-188 ◽  
Author(s):  
Gautam Chaurasia ◽  
Matthias Futschik
Keyword(s):  
Human Interactome

Machine Learning in Quantitative Protein–peptide Affinity Prediction: Implications for Therapeutic Peptide Design

2019 ◽  
Vol 20 (3) ◽  
pp. 170-176 ◽  
Author(s):  
Zhongyan Li ◽  
Qingqing Miao ◽  
Fugang Yan ◽  
Yang Meng ◽  
Peng Zhou
Keyword(s):  
Machine Learning ◽  
Binding Affinity ◽  
Peptide Binding ◽  
Machine Learning Techniques ◽  
Future Perspective ◽  
Peptide Design ◽  
Human Interactome ◽  
Therapeutic Peptide ◽  
Peptide Affinity ◽  
Peptide Binding Affinity

Background:Protein–peptide recognition plays an essential role in the orchestration and regulation of cell signaling networks, which is estimated to be responsible for up to 40% of biological interaction events in the human interactome and has recently been recognized as a new and attractive druggable target for drug development and disease intervention.Methods:We present a systematic review on the application of machine learning techniques in the quantitative modeling and prediction of protein–peptide binding affinity, particularly focusing on its implications for therapeutic peptide design. We also briefly introduce the physical quantities used to characterize protein–peptide affinity and attempt to extend the content of generalized machine learning methods.Results:Existing issues and future perspective on the statistical modeling and regression prediction of protein– peptide binding affinity are discussed.Conclusion:There is still a long way to go before establishment of general, reliable and efficient machine leaningbased protein–peptide affinity predictors.

scholarly journals Gene co-expression in the interactome: moving from correlation toward causation via an integrated approach to disease module discovery

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Paola Paci ◽  
Giulia Fiscon ◽  
Federica Conte ◽  
Rui-Sheng Wang ◽  
Lorenzo Farina ◽  
...  
Keyword(s):  
Network Analysis ◽  
Interaction Network ◽  
Integrated Approach ◽  
State Transitions ◽  
Disease Genes ◽  
Human Interactome ◽  
Protein Protein Interaction ◽  
Interactome Network ◽  
Module Discovery ◽  
Specific Disorders

AbstractIn this study, we integrate the outcomes of co-expression network analysis with the human interactome network to predict novel putative disease genes and modules. We first apply the SWItch Miner (SWIM) methodology, which predicts important (switch) genes within the co-expression network that regulate disease state transitions, then map them to the human protein–protein interaction network (PPI, or interactome) to predict novel disease–disease relationships (i.e., a SWIM-informed diseasome). Although the relevance of switch genes to an observed phenotype has been recently assessed, their performance at the system or network level constitutes a new, potentially fascinating territory yet to be explored. Quantifying the interplay between switch genes and human diseases in the interactome network, we found that switch genes associated with specific disorders are closer to each other than to other nodes in the network, and tend to form localized connected subnetworks. These subnetworks overlap between similar diseases and are situated in different neighborhoods for pathologically distinct phenotypes, consistent with the well-known topological proximity property of disease genes. These findings allow us to demonstrate how SWIM-based correlation network analysis can serve as a useful tool for efficient screening of potentially new disease gene associations. When integrated with an interactome-based network analysis, it not only identifies novel candidate disease genes, but also may offer testable hypotheses by which to elucidate the molecular underpinnings of human disease and reveal commonalities between seemingly unrelated diseases.

scholarly journals A Human Interactome in Three Quantitative Dimensions Organized by Stoichiometries and Abundances

Cell ◽  
2015 ◽  
Vol 163 (3) ◽  
pp. 712-723 ◽  
Author(s):  
Marco Y. Hein ◽  
Nina C. Hubner ◽  
Ina Poser ◽  
Jürgen Cox ◽  
Nagarjuna Nagaraj ◽  
...  
Keyword(s):  
Human Interactome

scholarly journals On the scope and limitations of baker's yeast as a model organism for studying human tissue-specific pathways

2014 ◽  
Author(s):  
Shahin Mohammadi ◽  
Baharak Saberidokht ◽  
Shankar Subramaniam ◽  
Ananth Grama
Keyword(s):  
Drug Targets ◽  
Model Organism ◽  
Functional Space ◽  
Computational Method ◽  
Therapeutic Interventions ◽  
Human Tissues ◽  
Human Interactome ◽  
Tissue Specific ◽  
Complex Disorders ◽  
Human Genes

Budding yeast, S. cerevisiae, has been used extensively as a model organism for studying cellular processes in evolutionarily distant species, including humans. However, different human tissues, while inheriting a similar genetic code, exhibit distinct anatomical and physiological properties. Specific biochemical processes and associated biomolecules that differentiate various tissues are not completely understood, neither is the extent to which a unicellular organism, such as yeast, can be used to model these processes within each tissue. We propose a novel computational and statistical framework to systematically quantify the suitability of yeast as a model organism for different human tissues. We develop a computational method for dissecting the human interactome into tissue-specific cellular networks. Using these networks, we simultaneously partition the functional space of human genes, and their corresponding pathways, based on their conservation both across species and among different tissues. We study these sub-spaces in detail, and relate them to the overall similarity of each tissue with yeast. Many complex disorders are driven by a coupling of housekeeping (universally expressed in all tissues) and tissue-selective (expressed only in specific tissues) dysregulated pathways. We show that human-specific subsets of tissue-selective genes are significantly associated with the onset and development of a number of pathologies. Consequently, they provide excellent candidates as drug targets for therapeutic interventions. We also present a novel tool that can be used to assess the suitability of the yeast model for studying tissue-specific physiology and pathophysiology in humans.

scholarly journals A 3D structural SARS-CoV-2–human interactome to explore genetic and drug perturbations

2021 ◽  
Author(s):  
Shayne D. Wierbowski ◽  
Siqi Liang ◽  
Yuan Liu ◽  
You Chen ◽  
Shagun Gupta ◽  
...  
Keyword(s):  
Human Interactome

scholarly journals MOSES: A New Approach to Integrate Interactome Topology and Functional Features for Disease Gene Prediction

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1713
Author(s):  
Manuela Petti ◽  
Lorenzo Farina ◽  
Federico Francone ◽  
Stefano Lucidi ◽  
Amalia Macali ◽  
...  
Keyword(s):  
Network Topology ◽  
Disease Gene ◽  
Gene Prediction ◽  
Knowledge Bases ◽  
Biological Knowledge ◽  
Disease Genes ◽  
Human Interactome ◽  
Disease Gene Prediction ◽  
Disease Associations ◽  
Functional Features

Disease gene prediction is to date one of the main computational challenges of precision medicine. It is still uncertain if disease genes have unique functional properties that distinguish them from other non-disease genes or, from a network perspective, if they are located randomly in the interactome or show specific patterns in the network topology. In this study, we propose a new method for disease gene prediction based on the use of biological knowledge-bases (gene-disease associations, genes functional annotations, etc.) and interactome network topology. The proposed algorithm called MOSES is based on the definition of two somewhat opposing sets of genes both disease-specific from different perspectives: warm seeds (i.e., disease genes obtained from databases) and cold seeds (genes far from the disease genes on the interactome and not involved in their biological functions). The application of MOSES to a set of 40 diseases showed that the suggested putative disease genes are significantly enriched in their reference disease. Reassuringly, known and predicted disease genes together, tend to form a connected network module on the human interactome, mitigating the scattered distribution of disease genes which is probably due to both the paucity of disease-gene associations and the incompleteness of the interactome.

scholarly journals Enriching human interactome with functional mutations to detect high-impact network modules underlying complex diseases

2019 ◽  
Author(s):  
Hongzhu Cui ◽  
Suhas Srinivasan ◽  
Dmitry Korkin
Keyword(s):  
Biological Networks ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Genetic Diseases ◽  
Detection Methods ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Human Interactome ◽  
Module Detection ◽  
Disease Module

AbstractProgress in high-throughput -omics technologies moves us one step closer to the datacalypse in life sciences. In spite of the already generated volumes of data, our knowledge of the molecular mechanisms underlying complex genetic diseases remains limited. Increasing evidence shows that biological networks are essential, albeit not sufficient, for the better understanding of these mechanisms. The identification of disease-specific functional modules in the human interactome can provide a more focused insight into the mechanistic nature of the disease. However, carving a disease network module from the whole interactome is a difficult task. In this paper, we propose a computational framework, DIMSUM, which enables the integration of genome-wide association studies (GWAS), functional effects of mutations, and protein-protein interaction (PPI) network to improve disease module detection. Specifically, our approach incorporates and propagates the functional impact of non-synonymous single nucleotide polymorphisms (nsSNPs) on PPIs to implicate the genes that are most likely influenced by the disruptive mutations, and to identify the module with the greatest impact. Comparison against state-of-the-art seed-based module detection methods shows that our approach could yield modules that are biologically more relevant and have stronger association with the studied disease. We expect for our method to become a part of the common toolbox for disease module analysis, facilitating discovery of new disease markers.

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