Topological Analysis and Sub-Network Mining of Protein-Protein Interactions

Author(s):  
Daniel Wu ◽  
Xiaohua Hu

In this chapter, we report a comprehensive evaluation of the topological structure of protein-protein interaction (PPI) networks, by mining and analyzing graphs constructed from the popular data sets publicly available to the bioinformatics research community. We compare the topology of these networks across different species, different confidence levels, and different experimental systems used to obtain the interaction data. Our results confirm the well-accepted claim that the degree distribution follows a power law. However, further statistical analysis shows that residues are not independent on the fit values, indicating that the power law model may be inadequate. Our results also show that the dependence of the average clustering coefficient on the vertices degree is far from a power law, contradicting many published results. For the first time, we report that the average vertex density exhibits a strong powder law dependence on the vertices degree for the networks studied, regardless of species, confidence levels, and experimental systems. We also present an efficient and accurate approach to detecting a community in a protein-protein interaction network from a given seed protein. Our experimental results show strong structural and functional relationships among member proteins within each of the communities identified by our approach, as verified by MIPS complex catalog database and annotations.

Author(s):  
Divya Dasagrandhi ◽  
Arul Salomee Kamalabai Ravindran ◽  
Anusuyadevi Muthuswamy ◽  
Jayachandran K. S.

Understanding the mechanisms of a disease is highly complicated due to the complex pathways involved in the disease progression. Despite several decades of research, the occurrence and prognosis of the diseases is not completely understood even with high throughput experiments like DNA microarray and next-generation sequencing. This is due to challenges in analysis of huge data sets. Systems biology is one of the major divisions of bioinformatics and has laid cutting edge techniques for the better understanding of these pathways. Construction of protein-protein interaction network (PPIN) guides the modern scientists to identify vital proteins through protein-protein interaction network, which facilitates the identification of new drug target and associated proteins. The chapter is focused on PPI databases, construction of PPINs, and its analysis.


2021 ◽  
Author(s):  
Hakimeh Khojasteh ◽  
Alireza Khanteymoori ◽  
Mohammad Hossein Olyaee

Background: SARS-CoV-2 pandemic first emerged in late 2019 in China. It has since infected more than 183 million individuals and caused about 4 million deaths globally. A protein-protein interaction network (PPIN) and its analysis can provide insight into the behavior of cells and lead to advance the procedure of drug discovery. The identification of essential proteins is crucial to understand for cellular survival. There are many centrality measures to detect influential nodes in complex networks. Since SARS-CoV-2 and (H1N1) influenza PPINs pose 553 common proteins. Analyzing influential proteins and comparing these networks together can be an effective step helping biologists in drug design. Results: We used 21 centrality measures on SARS-CoV-2 and (H1N1) influenza PPINs to identify essential proteins. PCA-based dimensionality reduction was applied on normalized centrality values. Some measures demonstrated a high level of contribution in comparison to others in both PPINs, like Barycenter, Decay, Diffusion degree, Closeness (Freeman), Closeness (Latora), Lin, Radiality, and Residual. Using validation measures, the appropriate clustering method was chosen for centrality measures. We also investigated some graph theory-based properties like the power law, exponential distribution, and robustness. Conclusions: Through analysis and comparison, both networks exhibited remarkable experimental results. The network diameters were equal and in terms of heterogeneity, SARS-CoV-2 PPIN tends to be more heterogeneous. Both networks under study display a typical power-law degree distribution. Dimensionality reduction and unsupervised learning methods were so effective to reveal appropriate centrality measures.


2021 ◽  
Author(s):  
Nikoleta Vavouraki ◽  
James E. Tomkins ◽  
Eleanna Kara ◽  
Henry Houlden ◽  
John Hardy ◽  
...  

AbstractThe Hereditary Spastic Paraplegias are a group of neurodegenerative diseases characterized by spasticity and weakness in the lower body. Despite the identification of causative mutations in over 70 genes, the molecular aetiology remains unclear. Due to the combination of genetic diversity and variable clinical presentation, the Hereditary Spastic Paraplegias are a strong candidate for protein-protein interaction network analysis as a tool to understand disease mechanism(s) and to aid functional stratification of phenotypes. In this study, experimentally validated human protein-protein interactions were used to create a protein-protein interaction network based on the causative Hereditary Spastic Paraplegia genes. Network evaluation as a combination of both topological analysis and functional annotation led to the identification of core proteins in putative shared biological processes such as intracellular transport and vesicle trafficking. The application of machine learning techniques suggested a functional dichotomy linked with distinct sets of clinical presentations, suggesting there is scope to further classify conditions currently described under the same umbrella term of Hereditary Spastic Paraplegias based on specific molecular mechanisms of disease.


2004 ◽  
Vol 5 (2) ◽  
pp. 173-178 ◽  
Author(s):  
Javier De Las Rivas ◽  
Alberto de Luis

In recent years, the biomolecular sciences have been driven forward by overwhelming advances in new biotechnological high-throughput experimental methods and bioinformatic genome-wide computational methods. Such breakthroughs are producing huge amounts of new data that need to be carefully analysed to obtain correct and useful scientific knowledge. One of the fields where this advance has become more intense is the study of the network of ‘protein–protein interactions’, i.e. the ‘interactome’. In this short review we comment on the main data and databases produced in this field in last 5 years. We also present a rationalized scheme of biological definitions that will be useful for a better understanding and interpretation of ‘what a protein–protein interaction is’ and ‘which types of protein–protein interactions are found in a living cell’. Finally, we comment on some assignments of interactome data to defined types of protein interaction and we present a new bioinformatic tool called APIN (Agile Protein Interaction Network browser), which is in development and will be applied to browsing protein interaction databases.


2015 ◽  
Vol 2015 ◽  
pp. 1-9
Author(s):  
Peng Liu ◽  
Lei Yang ◽  
Daming Shi ◽  
Xianglong Tang

A method for predicting protein-protein interactions based on detected protein complexes is proposed to repair deficient interactions derived from high-throughput biological experiments. Protein complexes are pruned and decomposed into small parts based on the adaptivek-cores method to predict protein-protein interactions associated with the complexes. The proposed method is adaptive to protein complexes with different structure, number, and size of nodes in a protein-protein interaction network. Based on different complex sets detected by various algorithms, we can obtain different prediction sets of protein-protein interactions. The reliability of the predicted interaction sets is proved by using estimations with statistical tests and direct confirmation of the biological data. In comparison with the approaches which predict the interactions based on the cliques, the overlap of the predictions is small. Similarly, the overlaps among the predicted sets of interactions derived from various complex sets are also small. Thus, every predicted set of interactions may complement and improve the quality of the original network data. Meanwhile, the predictions from the proposed method replenish protein-protein interactions associated with protein complexes using only the network topology.


2013 ◽  
Vol 11 (01) ◽  
pp. 1340005 ◽  
Author(s):  
BJÖRN SOMMER ◽  
BENJAMIN KORMEIER ◽  
PAVEL S. DEMENKOV ◽  
PATRIZIO ARRIGO ◽  
KLAUS HIPPE ◽  
...  

The CELLmicrocosmos PathwayIntegration (CmPI) was developed to support and visualize the subcellular localization prediction of protein-related data such as protein-interaction networks. From the start it was possible to manually analyze the localizations by using an interactive table. It was, however, quite complicated to compare and analyze the different localization results derived from data integration as well as text-mining-based databases. The current software release provides a new interactive visual workflow, the Subcellular Localization Charts. As an application case, a MUPP1-related protein-protein interaction network is localized and semi-automatically analyzed. It will be shown that the workflow was dramatically improved and simplified. In addition, it is now possible to use custom protein-related data by using the SBML format and get a view of predicted protein localizations mapped onto a virtual cell model.


2021 ◽  
Vol 3 (2) ◽  
pp. 25-34
Author(s):  
Hilmi Farhan Ramadhani ◽  
Annisa ◽  
Wisnu Ananta Kusuma

Coronavirus Disease 2019 (COVID-19) will cause disease complications and organ damage due to excessive inflammatory reactions if left untreated. Computational analysis of protein-protein interactions can be carried out in various ways, including topological analysis and clustering of protein-protein interaction networks. Topological analysis can identify significant proteins by measuring the most important nodes with centrality measurements. By using Principal Component Analysis (PCA), the types of centrality measures were extracted into the overall centrality value. The study aimed to found significant proteins in COVID-19 protein-protein interactions using PCA and ClusterONE. This study used 57 proteins associated with COVID-19 to obtain protein networks. All of these proteins are homo sapiens organism. The number of proteins and the number of interactions from 57 proteins were 357 proteins and 1686 interactions. The results of this study consisted of two clusters; the best cluster was the first cluster with a lower p-value but had an average overall centrality value that closed to the second clus-ter. There are twenty important proteins in that cluster, and all of these proteins are related to COVID-19. These proteins are expected to be used in the process of discovering medicinal compounds in COVID-19


2012 ◽  
Vol 22 (1) ◽  
pp. 7-14
Author(s):  
Bui Phuong Thuy ◽  
Trinh Xuan Hoang

Protein interacts with one another resulting in complex functions in living organisms. Like many other real-world networks, the networks of protein-protein interactions possess a certain degree of ordering, such as the scale-free property. The latter means that the probability $P$ to find a protein that interacts with $k$ other proteins follows a power law, $P(k) \sim k^{-\gamma}$. Protein interaction networks (PINs) have been studied by using a stochastic model, the duplication-divergence model, which is based on mechanisms of gene duplication and divergence during evolution. In this work, we show that this model can be used to fit experimental data on the PIN of yeast Saccharomyces cerevisae at two different time instances simultaneously. Our study shows that the evolution of PIN given by model is consistent with growing experimental data over time, and that the scale-free property of protein interaction network is robust against random deletion of interactions.


Author(s):  
Yu-Miao Zhang ◽  
Jun Wang ◽  
Tao Wu

In this study, the Agrobacterium infection medium, infection duration, detergent, and cell density were optimized. The sorghum-based infection medium (SbIM), 10-20 min infection time, addition of 0.01% Silwet L-77, and Agrobacterium optical density at 600 nm (OD600), improved the competence of onion epidermal cells to support Agrobacterium infection at >90% efficiency. Cyclin-dependent kinase D-2 (CDKD-2) and cytochrome c-type biogenesis protein (CYCH), protein-protein interactions were localized. The optimized procedure is a quick and efficient system for examining protein subcellular localization and protein-protein interaction.


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