BackgroundBiological networks connect genes, gene products to one another. A network of co-regulated genes may form gene clusters that can encode proteins and take part in common biological processes. A gene co-expression network describes inter-relationships among genes. Existing techniques generally depend on proximity measures based on global similarity to draw the relationship between genes. It has been observed that expression profiles are sharing local similarity rather than global similarity. We propose an expression pattern based method called GeCON to extract Gene CO-expression Network from microarray data. Pair-wise supports are computed for each pair of genes based on changing tendencies and regulation patterns of the gene expression. Gene pairs showing negative or positive co-regulation under a given number of conditions are used to construct such gene co-expression network. We construct co-expression network with signed edges to reflect up- and down-regulation between pairs of genes. Most existing techniques do not emphasize computational efficiency. We exploit a fast correlogram matrix based technique for capturing the support of each gene pair to construct the network.ResultsWe apply GeCON to both real and synthetic gene expression data. We compare our results using the DREAM (Dialogue for Reverse Engineering Assessments and Methods) Challenge data with three well known algorithms, viz., ARACNE, CLR and MRNET. Our method outperforms other algorithms based on in silico regulatory network reconstruction. Experimental results show that GeCON can extract functionally enriched network modules from real expression data.ConclusionsIn view of the results over several in-silico and real expression datasets, the proposed GeCON shows satisfactory performance in predicting co-expression network in a computationally inexpensive way. We further establish that a simple expression pattern matching is helpful in finding biologically relevant gene network. In future, we aim to introduce an enhanced GeCON to identify Protein-Protein interaction network complexes by incorporating variable density concept.
The development of therapeutic targets for COVID-19 treatment relies on understanding the molecular mechanism of pathogenesis. Identifying genes and proteins involved in the infection mechanism is the key to shedding light on the complex molecular mechanisms. The combined effort of many laboratories distributed throughout the world has produced protein and genetic interactions. We integrated available results and obtained a host protein-protein interaction network composed of 1432 human proteins. Next, we performed network centrality analysis to identify critical proteins in the derived network. Finally, we performed a functional enrichment analysis of central proteins. We observed that the identified proteins are primarily associated with several crucial pathways, including cellular process, signaling transduction, neurodegenerative diseases. We focused on the proteins that are involved in human respiratory tract diseases. We highlighted many potential therapeutic targets, including RBX1, HSPA5, ITCH, RAB7A, RAB5A, RAB8A, PSMC5, CAPZB, CANX, IGF2R, HSPA1A, which are central and also associated with multiple diseases.
Motivation
The outbreak of novel severe acute respiratory syndrome coronavirus (SARS-CoV-2, also known as COVID-19) in Wuhan has attracted worldwide attention. SARS-CoV-2 causes severe inflammation, which can be fatal. Consequently, there has been a massive and rapid growth in research aimed at throwing light on the mechanisms of infection and the progression of the disease. With regard to this data science is playing a pivotal role in in silico analysis to gain insights into SARS-CoV-2 and the outbreak of COVID-19 in order to forecast, diagnose and come up with a drug to tackle the virus. The availability of large multiomics, radiological, bio-molecular and medical datasets requires the development of novel exploratory and predictive models, or the customisation of existing ones in order to fit the current problem. The high number of approaches generates the need for surveys to guide data scientists and medical practitioners in selecting the right tools to manage their clinical data.
Results
Focusing on data science methodologies, we conduct a detailed study on the state-of-the-art of works tackling the current pandemic scenario. We consider various current COVID-19 data analytic domains such as phylogenetic analysis, SARS-CoV-2 genome identification, protein structure prediction, host–viral protein interactomics, clinical imaging, epidemiological research and drug discovery. We highlight data types and instances, their generation pipelines and the data science models currently in use. The current study should give a detailed sketch of the road map towards handling COVID-19 like situations by leveraging data science experts in choosing the right tools. We also summarise our review focusing on prime challenges and possible future research directions.
Contact
hguzzi@unicz.it, sroy01@cus.ac.in
SARS-CoV-2 is mutating and creating divergent variants across the world. An in-depth investigation of the amino acid substitutions in the genomic signature of SARS-CoV-2 proteins is highly essential for understanding its host adaptation and infection biology. A total of 9587 SARS-CoV-2 structural protein sequences collected from 49 different countries are used to characterize protein-wise variants, substitution patterns (type and location), and major substitution changes. The majority of the substitutions are distinct, mostly in a particular location, and leads to a change in amino acid's biochemical properties. In terms of mutational changes, Envelope (E) and Membrane (M) proteins are relatively stable than Nucleocapsid (N) and Spike (S) proteins. Several co-occurrence substitutions are observed, particularly in S and N proteins. Substitution specific to active sub-domains reveals that Heptapeptide Repeat, Fusion peptides, Transmembrane in S protein, and N-terminal and C-terminal domains in N protein are remarkably mutated. We also observe a few deleterious mutations in the above domains. The overall study on non-synonymous mutation in structural proteins of SARS-CoV-2 at early in the pandemic indicates a diversity amongst virus sequences.
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