Biology subjects

Saha, S.

Publications and source records attributed to Saha, S..

At least 163 records · Page 9Linked to original sources

bioRxiv2021

Genomic identification, annotation, and comparative analysis of Vacuolar-type ATP synthase subunits in Diaphorina citri

Detailed annotation and comparative analysis were performed on the Asian citrus psyllid (ACP), Diaphorina citri, vacuolar-type ATP synthase (V-ATPase) to support the biological understanding and development of novel therapeutics to manage psyllid vectors. D. citri is a hemipteran insect that vectors the causative agent, the bacteria Candidatus Liberibacter asiaticus (CLas), of the citrus greening disease, Huanglongbing (HLB). Millions of citrus trees have been destroyed by citrus greening and every grove in Florida has been directly impacted. In eukaryotic organisms, V-ATPase is an abundant heterodimeric enzyme that serves the cell with essential compartment acidification through the active processes that transport protons across the membrane. Manual curation was completed on 15 putative V-ATPase genes in the D. citri genome. Comparative genomic analysis reveals that the D. citri V-ATPase subunits share domains and motifs with other insects, including the V-ATPase-A superfamily domain from the V-ATPase catalytic subunit A, which shares a 92% identity with Acyrthosiphon pisum. Phylogenetic analysis separates D. citri V-ATPase subunits into expected clades with orthologous sequences. Based on the results of annotation and comparative genomic analysis, RNAi therapies targeting D. citri V-ATPase genes, which have been successfully utilized in related hemipterans, are being pursued. Annotation of the D. citri genome is a critical step towards the development of directed-pest management that will lead to the reduced spread of the pathogens causing HLB throughout the citrus industry.

bioinformatics↗

bioRxiv2021

Ubiquitin Proteasome Pathway annotation in Diaphorina citri can reveal potential targets for RNAi based pest management

Ubiquitination is an ATP-dependent process that targets proteins for degradation by the proteasome. In this study, we annotated 15 genes from the ubiquitin-proteasome pathway in the Asian citrus psyllid, Diaphorina citri. This psyllid vector has come to prominence in the last decade due to its role in the transmission of the devastating bacterial pathogen, Candidatus Liberibacter asiaticus (CLas). Infection of citrus crops by this pathogen causes Huanglongbing (HLB or citrus greening disease) and results in the eventual death of citrus trees. The identification and correct annotation of these genes in D. citri will be useful for functional genomic studies that aid in the development of RNAi-based management strategies aimed at reducing the spread of HLB. Investigating the effects of CLas infection on the expression of ubiquitin-proteasome pathway genes may provide new information regarding the role that these genes play in the acquisition and transmission of CLas by D. citri.

bioinformatics↗

bioRxiv2021

Annotation of glycolysis, gluconeogenesis, and trehaloneogenesis pathways provide insight into carbohydrate metabolism in the Asian citrus psyllid

Citrus greening disease is caused by the pathogen Candidatus Liberibacter asiaticus, which is transmitted by the Asian citrus psyllid, Diaphorina citri. There is no curative treatment or significant prevention mechanism for this detrimental disease that causes continued economic losses from reduced citrus production. A high quality genome of D. citri is being manually annotated to provide accurate gene models required to identify novel control targets and increase understanding of this pest. Here, we annotated genes involved in glycolysis, gluconeogenesis, and trehaloneogenesis in the D. citri genome, as these are core metabolic pathways and suppression could reduce this pest. Specifically, twenty-five genes were identified and annotated in the glycolysis and gluconeogenesis pathways and seven genes for the trehaloneogenesis pathway. Comparative analysis showed that the glycolysis genes in D. citri are highly conserved compared to orthologs in other insect systems, but copy numbers vary in D. citri. Expression levels of the annotated gene models were analyzed and several enzymes in the glycolysis pathway showed high expression in the thorax. This is consistent with the primary use of glucose by flight muscles located in the thorax. A few of the genes annotated in D. citri have been targeted for gene knockdown as a proof of concept, for RNAi therapeutics. Thus, manual annotation of these core metabolic pathways provides accurate genomic foundations for developing gene-targeting therapeutics to reduce D. citri.

bioinformatics↗

bioRxiv2021

Waning grasslands: a quantitative temporal evaluation of the grassland habitats across human-dominated upper Gangetic Plains, north India

Grassland habitats currently face severe anthropogenic exploitations leading to cascading effects on the survival of grassland-dependent biodiversity globally, particularly in non-protected areas. Significant amount of such biodiversity-rich grasslands in India are found outside protected areas but lack quantitative information on their status. We evaluated the current and historical (30 years) status of the grasslands using a combination of intensive field surveys and GIS tools across one of the most fertile, human-dominated region: the upper Gangetic Plains of north India. On-ground mapping and visual classifications revealed 57% decline in grassland habitats between 1985 (418 km2) and 2015 (178km2), mostly driven by conversion to croplands (74% contribution). Radio-telemetry data from the largest endemic cervid swamp deer (n=2) showed grassland-dominated average home range (50% BBMM) size of 1.02 km2. The animals highly preferred these patches (average Ivlevs index- 0.85) and showed highest temporal continuity (88%) compared to other LULC classes. Camera trapping within the core habitats suggests critical use of these patches as fawning/breeding grounds. Habitat suitability analysis indicates only [~]18% of the entire area along Ganges is suitable for swamp deer. Accurate mapping (86% accuracy) and characterization of four major grass species revealed a total 144.04 km{superscript 2} vegetation area, dominted by Saccharum sp. (35%). We recommend protection and recovery of these critical grassland patches to maintain dynamic corridors and other appropriate management strategies involving multiple stakeholders to ensure survival of this critical ecosystem. Such evaluations, if spatially expanded, would be critical to restore this rapidly vanishing ecosystem worldwide.

ecology↗

bioRxiv2021

Annotation of Putative Circadian Rhythm-Associated Genes in Diaphorina citri (Hemiptera : Liviidae)

The circadian rhythm is a process involving multiple genes that generates an internal molecular clock, allowing organisms to anticipate environmental conditions produced by the earths rotation on its axis. This report presents the results of the manual curation of twenty-seven genes likely associated with circadian rhythm in the genome of Diaphorina citri, the Asian citrus psyllid. This insect acts as the vector of the bacterial pathogen Candidatus Liberibacter asiaticus (CLas), the causal agent of citrus greening disease (Huanglongbing). This disease is the most severe detriment to citrus industries and has drastically decreased crop yields worldwide. Based on the genes identified in the psyllid genome, namely cry1 and cry2, D. citri likely possesses a circadian model similar to that of the lepidopteran butterfly, Danaus plexippus. Manual annotation of these genes will allow future molecular therapeutics to be developed that can disrupt the psyllid biology.

bioinformatics↗

bioRxiv2021

Annotation of Hox cluster and Hox cofactor genes in the Asian citrus psyllid, Diaphorina citri, reveals novel features

Hox genes and their cofactors are essential developmental genes that specify regional identity in animals, including insects. A particularly interesting feature of Hox genes is their conserved arrangement in clusters in the same order in which they specify identity along the anterior-posterior axis. Among insects, breaks in the cluster have been reported in a few species, but these seem to be the exception rather than the rule. We have annotated the ten Hox genes of the Asian citrus psyllid, Diaphorina citri, and determined that there is a split in its Hox cluster between the Deformed and Sex combs reduced genes. This is the first time a break at this position has been observed in an insect Hox cluster. We have also annotated the D. citri orthologs of the Hox cofactor genes homothorax, PKNOX and extradenticle. Interestingly, we found an additional copy of extradenticle in D. citri that appears to be a retrogene. Expression data and sequence conservation suggest that the extradenticle retrogene may have retained the original extradenticle function and allowed the parental extradenticle gene to diverge.

bioinformatics↗

bioRxiv2021

Viroporin activity of SARS-CoV-2 Orf3a and Envelope protein impacts viral pathogenicity

COVID-19 is caused by SARS-CoV-2 which has so far affected more than 500 million people worldwide and killed over 6 million as of 1st May, 2022. The approved emergency-use vaccines were lifesaving to such a devastating pandemic. Viroporins are important players of the life cycle of SARS-CoV-2 and are primary to its pathogenesis. We studied the two prominent viroporins of SARS-CoV-2 (i) Orf3a and (ii) Envelope (E) protein from a sequential and structural point of view. Orf3a is a cation selective viral ion channel which has been shown to disrupt the endosomal pathways. E protein is one of the most conserved proteins among the SARS-CoV proteome which affects the ERGIC related pathways. The aqueous medium through the viroporins mediates the non-selective translocation of cations, affecting ionic homeostasis in the host cellular compartments. This ionic imbalance could potentially lead to increased inflammatory response in the host cell. Our results shed light into the mechanism of viroporin action, which can be potentially leveraged for the development of antiviral therapeutics. Our results corroborate with previously published transcriptomic data from COVID-19 infected lung alveolar cells where inflammatory responses and molecular regulators directly impacted by ion channelling were upregulated.

molecular biology↗

bioRxiv2021

Quantification of new and archived Diaphorina citri transcriptome data using a chromosomal length D. citri genome assembly reveals the vector's tissue-specific transcriptional response to citrus greening disease

Background Huanglongbing (HLB) is the most serious disease of citrus. HLB is caused by the obligate, intracellular bacterium "Candidatus Liberibacter asiaticus" (CLas). CLas is transmitted by Diaphorina citri, the Asian citrus psyllid. Development of transmission blocking strategies to manage HLB relies on knowledge of CLas-D. citri interactions at the molecular level. Prior transcriptome analyses of CLas-infected and un-infected D. citri point to changes in psyllid biology due to CLas-infection. These studies relied on incomplete versions of the D. citri genome, lacked proper host plant controls, and/or were analyzed using different statistical approaches. Therefore, we used standardized experimental and computational approaches to identify differentially expressed genes in both CLas (+) and CLas (-) D. citri. The comparative analysis utilized the newest chromosomal length D. citri genome assembly Diaci_v3. In this work, we present a quantitative transcriptome analysis of excised heads, salivary glands, midguts and bacteriomes from CLas (+) and CLas (-) insects. Results Each organ had unique transcriptome profiles and responses to CLas infection. Though most psyllids were infected with CLas, CLas-derived transcripts were not detected in all organs. By analyzing the midgut dataset using both the Diaci_v1.1 and v3.0 D. citri genomes, we showed that improved genome assembly led to significant and quantifiable differences in RNAseq data interpretation. Conclusions Our results support the hypothesis that future transcriptome studies on circulative, vector-borne pathogens should be conducted at the tissue specific level using complete, chromosomal-length genome assemblies for the most accurate understanding of pathogen-induced changes in vector gene expression.

genomics↗

bioRxiv2021

Benchmarking of a Bayesian single cell RNAseq differential gene expression test for dose-response study designs.

The application of single-cell RNA sequencing (scRNAseq) for the evaluation of chemicals, drugs, and food contaminants presents the opportunity to consider cellular heterogeneity in pharmacological and toxicological responses. Current differential gene expression analysis (DGEA) methods focus primarily on two group comparisons, not multi-group dose-response study designs used in safety assessments. To benchmark DGEA methods for dose-response scRNAseq experiments, we proposed a multiplicity corrected Bayesian testing approach and compare it against 8 other methods including two frequentist fit-for-purpose tests using simulated and experimental data. Our Bayesian test method outperformed all other tests for a broad range of accuracy metrics including control of false positive error rates. Most notable, the fit-for-purpose and standard multiple group DGEA methods were superior to the two group scRNAseq methods for dose-response study designs. Collectively, our benchmarking of DGEA methods demonstrates the importance in considering study design when determining the most appropriate test methods.

genomics↗

bioRxiv2021

BCN057, a Modulator of GSK3b Induces KRAS G12D Mutant Pancreatic Cancer Cell Death

Effective treatment for Pancreatic Cancer remains a major challenge due to its resistance to radiation/chemotherapy and poor drug permeability. Moreover, treatment induced normal tissue toxicity, mainly to the duodenum and gastrointestinal epithelium, is common and is a dose limiting event, while toxicity to the pancreas is relatively rare1-3. Gastrointestinal toxicity, however, often results in interruption, reduction or premature withdrawal of anti-cancer therapy which is a very significant factor impacting the overall survival of patients being treated. Therefore, development of a therapeutic strategy to selectively sensitize tumor tissue without inducing normal tissue toxicity is important. In this manuscript, we show that the novel small molecule BCN057 can modulate chemo-sensitivity of oncogenic RAS pancreatic cancer cells while conversely protecting normal intestinal epithelium from off target toxicity. In particular, BCN 057 protects Lgr5 positive intestinal stem cells, thereby preserving barrier function. Further, it is demonstrated that BCN057 inhibits GSK3{beta} and thereby induces a pro-apoptotic phosphorylation pattern on c-Jun in KRAS G12D mutant pancreatic cancer cells (Panc-1) leading to the restoration of PTEN expression and consequent apoptosis. This appears to be a new mechanistic observation for the oncogenic RAS phenotype. Lastly, concurrent with its GSK3{beta} inhibition, BCN057 is a small molecule inhibitor of PD-1 expression on human T-lymphocytes co-cultured with human pancreatic cancer cells. In summary, BCN057 can promote synthetic lethality specifically to malignant cells and therefore should be considered to improve the therapeutic ratio in pancreatic and epithelial cancer treatment in conjunction with chemotherapy and radiation.

cancer biology↗

bioRxiv2021

scSGL: Signed Graph Learning for Single-Cell Gene Regulatory Network Inference

MotivationElucidating the topology of gene regulatory networks (GRNs) from large single-cell RNA sequencing (scRNAseq) datasets, while effectively capturing its inherent cell-cycle heterogeneity and dropouts, is currently one of the most pressing problems in computational systems biology. Recently, graph learning (GL) approaches based on graph signal processing (GSP) have been developed to infer graph topology from signals defined on graphs. However, existing GL methods are not suitable for learning signed graphs, which represent a characteristic feature of GRNs, as they account for both activating and inhibitory relationships between genes. They are also incapable of handling high proportion of zero values, which represent dropouts in single cell experiments. To this end, we propose a novel signed GL approach, scSGL, that learns GRNs based on the assumption of the smoothness and non-smoothness of gene expressions over activating and inhibitory edges, respectively. scSGL is then extended with kernels to take the nonlinearity of co-expressions into account and handle high proportion of dropouts. From GSP perspective, this extension corresponds to assuming smoothness/non-smoothness of graph signals in a higher dimensional space defined by the kernel. The proposed approach is formulated as a non-convex optimization problem and solved using an efficient ADMM framework. ResultsIn our experiments on simulated and real single cell datasets, scSGL compares favorably with other single cell gene regulatory network reconstruction algorithms. AvailabilityThe scSGL code and analysis scripts are available at (https://github.com/Single-Cell-Graph-Learning/scSGL).

bioinformatics↗

bioRxiv2021

Distinct MUNC lncRNA structural domains regulate transcription of different promyogenic factors

Many lncRNAs have been discovered using transcriptomic data, however, it is broadly unclear what fraction of lncRNAs are functional and what structural properties affect their phenotype. MUNC lncRNA, also known as DRReRNA, stimulates skeletal muscle differentiation. The prevailing hypothesis is that MUNC stimulates the Myod1 gene in cis as an enhancer RNA and stimulates expression of several other promyogenic genes in trans by recruiting the cohesin complex to their promoters. Experimental probing of the RNA structure revealed that MUNC contains multiple structural domains not detected by RNA structure prediction algorithms in the absence of experimental information. We discovered that these specific and structurally distinct domains are required for induction of different promyogenic genes, for binding at different genomic sites to regulate the expression of adjacent genes, and for binding the cohesin complex. Moreover, we found that induction of Myod1 or interaction with cohesin comprise only a subset of the broad regulatory impact of this lncRNA. Our study thus reveals unexpectedly complex, structure-driven functions for the MUNC lncRNA and emphasizes the importance of experimentally determined structures for understanding structure-function relationships in lncRNAs.

molecular biology↗

bioRxiv2021

Workflows for rapid functional annotation of diverse arthropod genomes

Genome sequencing of a diverse array of arthropod genomes is already underway and these genomes will be used to study human health, agriculture, biodiversity and ecology. These new genomes are intended to serve as community resources and provide the foundational information that is required to apply omics technologies to a more diverse set of species. However, biologists require genome annotation to use these genomes and derive a better understanding of complex biological systems. Genome annotation incorporates two related but distinct processes: demarcating genes and other elements present in genome sequences (structural annotation); and associating function with genetic elements (functional annotation). While there are well established and freely available workflows for structural annotation of gene identification in newly assembled genomes, workflows for providing the functional annotation required to support functional genomics studies are less well understood. Genome-scale functional annotation is required for functional modeling (enrichment, networks, etc.) and a first-pass genome-wide functional annotation effort can rapidly identify under-represented gene sets for focused community annotation efforts. We present an open source, open access and containerized pipeline for genome-scale functional annotation of insect proteomes and apply it to a diverse range of arthropod species. We show that the performance of the predictions is consistent across a set of arthropod genomes with varying assembly and annotation quality.Complete instructions for running each component of the functional annotation pipeline on the command line, a high performance computing cluster and the CyVerse Discovery Environment can be found at the readthedocs site (https://agbase-docs.readthedocs.io/en/latest/agbase/workflow.html). Simple summaryGenomic technologies are accumulating information about genes at a faster rate than ever before, and sequencing initiatives like the Earth Biogenome Project, i5k and Ag100Pest are expected to increase this rate of acquisition. However, if genomic sequencing is to be used for improvement of human health, agriculture and our understanding of biological systems, it is necessary to identify genes and understand how they contribute to biological outcomes. While there are several well-established workflows for assembling genomic sequences and identifying genes, understanding gene function is essential to create actionable knowledge. Moreover this functional annotation process must be easily accessible and provide information at a genomic scale to keep up with new sequence data. We report a well defined workflow for rapid functional annotation of whole proteomes to produce Gene Ontology and pathways information. We test this workflow on a diverse set of arthropod genomes and compare it to common arthropod reference genomes. The workflow we described is freely and publicly available via a web interface on CyVerse or as biocontainers that can be deployed scalably on local computing systems.

bioinformatics↗

bioRxiv2021

Genetic architecture of natural variations of cardiac performance in flies

Deciphering the genetic architecture of human cardiac disorders is of fundamental importance but their underlying complexity is a major hurdle. We investigated the natural variation of cardiac performance in the sequenced inbred lines of the Drosophila Genetic Reference Panel (DGRP). Genome Wide Associations Studies (GWAS) identified genetic networks associated with natural variation of cardiac traits which were used to gain insights as to the molecular and cellular processes affected. Non-coding variants that we identified were used to map potential regulatory non-coding regions, which in turn were employed to predict Transcription Factors (TFs) binding sites. Cognate TFs, many of which themselves bear polymorphisms associated with variations of cardiac performance, were also validated by heart specific knockdown. Additionally, we showed that the natural variations associated with variability in cardiac performance affect a set of genes overlapping those associated with average traits but through different variants in the same genes. Furthermore, we showed that phenotypic variability was also associated with natural variation of gene regulatory networks. More importantly, we documented correlations between genes associated with cardiac phenotypes in both flies and humans, which supports a conserved genetic architecture regulating adult cardiac function from arthropods to mammals. Specifically, roles for PAX9 and EGR2 in the regulation of the cardiac rhythm were established in both models, illustrating that the characteristics of natural variations in cardiac function identified in Drosophila can accelerate discovery in humans.

genetics↗

bioRxiv2021

A tumor suppressive long noncoding RNA, DRAIC, inhibits protein translation and induces autophagy by activating AMPK

LncRNAs are long RNA transcripts that do not code for proteins and that have been shown to play a major role in cellular processes through diverse mechanisms. DRAIC, a lncRNA which is downregulated in castration-resistant advanced prostate cancer, inhibits the NF-kB pathway by inhibiting the I{kappa}B kinase. Decreased DRAIC expression predicted poor patient outcome in gliomas and seven other cancers. We now report that DRAIC suppresses invasion, migration, colony formation and xenograft growth of glioblastoma derived cell lines. DRAIC activates AMPK by downregulating the NF-{kappa}B target gene GLUT1, and thus represses mTOR, leading to downstream effects such as decrease in protein translation and increase in autophagy. DRAIC, therefore, has an effect on multiple signal transduction pathways that are important for oncogenesis: the NF-{kappa}B pathway and AMPK-mTOR-S6K/ULK1 pathway. The regulation of NF-{kappa}B, protein translation and autophagy by the same lncRNA explains the tumor suppressive role of DRAIC in different cancers and reinforces the importance of lncRNAs as emerging regulators of signal transduction pathways.

cancer biology↗

bioRxiv2021

Quorum sensing signals from epibiont mediate the induction of bioactive peptides in mat-forming cyanobacteria Nostoc

The regulation of oligopeptides production is essential in understanding their ecological role in complex microbial communities including harmful cyanobacterial blooms. The role of chemical communication between the cyanobacterium and the microbial community harboured as epibionts within its phycosphere is at an initial stage of research and little is understood about its specificity. Herein, we present insight into the role of a bacterial epibiont in regulating production of cyanobacterial oligopeptides microviridins, well-known elastase inhibitors with presumed anti-grazing effects, in an ecologically important cyanobacterial genus Nostoc. Heterologous expression and identification of specific signal molecules from the epibiont suggest the role of a quorum sensing-based interaction. Further, physiological experiments show an increase in microviridin production without affecting cyanobacterial growth and photosynthetic activity. Simultaneously, oligopeptides presenting a selective inhibition pattern provide support for their specific function in response to the presence of cohabitant epibionts. Thus, the chemical interaction revealed in our study provides an example of an interspecies signalling pathway monitoring the bacterial flora around the cyanobacterial filaments and induction of intrinsic species-specific metabolic responses. IMPORTANCEThe regulation of cyanopeptide production beyond microcystin is essential to understand their ecological role in complex microbial communities, e.g. harmful cyanobacterial blooms. The role of chemical communication between the cyanobacterium and the epibionts within its phycosphere is at an initial stage of research and little is understood about its specificity. The frequency of cyanopeptide occurrence also demonstrates the need to understand the contribution of cyanobacterial peptides to the overall biological impact of cyanopeptides on aquatic organisms and vertebrates including humans. Our results shed light on the epibiont control of cyanopeptide production via quorum sensing mechanisms and we posit that such mechanisms may be widespread in natural cyanobacterial bloom community regulation.

microbiology↗

bioRxiv2021

Genomic surveillance and phylodynamic analyses reveal emergence of novel mutation and co-mutation patterns within SARS-CoV2 variants prevalent in India

Emergence of distinct viral clades has been observed in SARS-CoV2 variants across the world and India. Identification of the genomic diversity and the phylodynamic profiles of the prevalent strains of the country are critical to understand the evolution and spread of the variants. We performed whole-genome sequencing of 54 SARS-CoV2 strains collected from COVID-19 patients in Kolkata, West Bengal during August to October 2020. Phylogeographic and phylodynamic analyses were performed using these 54 and other sequences from India and abroad available in GISAID database. Spatio-temporal evolutionary dynamics of the pathogen across various regions and states of India over three different time periods in the year 2020 were analyzed. We estimated the clade dynamics of the Indian strains and compared the clade specific mutations and the co-mutation patterns across states and union territories of India over the time course. We observed that GR, GH and G (GISAID) or 20B and 20A (Nextstrain) clades were the prevalent clades in India during middle and later half of the year 2020. However, frequent mutations and co-mutations observed within the major clades across time periods do not show much overlap, indicating emergence of newer mutations in the viral population prevailing in the country. Further, we explored the possible association of specific mutations and co-mutations with the infection outcomes manifested within the Indian patients.

genomics↗

bioRxiv2021

The Central Importance of Hub Proteins in a Disease-Gene Network Model: A New Paradigm of Chronic Myeloid Leukemia Disease Study

BackgroundThe network biology of disease-gene association provides a holistic framework to decipher the intrinsic complexity of disease signaling pathways into cellular communication level. Different types of studies including large-scale genome-wide association, multifactor dimensional reduction analysis, whole genome, or exome-based sequencing strategies of diseases are striving to connect genes to diseases. Indeed, these approaches have had some accomplishments, but the cellular communication level needs a more streamlining outcome to understand the mechanistic impact of context. The higher-order combination of disease-gene interaction has a great potential to decipher the intricateness of diseases. The molecular interaction pattern of diseases at the genomic and proteomic level offers a revolutionized platform not only to understand the complexity of particular disease modules and pathways but also leading towards design novel therapeutics. ResultsThe enrichment and topology analysis was performed by JEPETTO a plugin of Cytoscape software. We identified the chronic myeloid leukemia (CML) disease signaling pathways that appeared first in the ranking order based on XD-score among the bone, breast, and colon genes set and second at kidney and liver. This result validates the highest proximity between CML and five cancerous tissue gene set clusters. The topology analysis also supports the results while (p<0.0001) is considered to be extremely significant between CML and fives cancerous tissues genes set. Enrichment analysis identified that abl-gene acts as an overlapping node which is the major gene for inducing various mutations in CML. Amazingly, we identified 56 common path expansion/added genes among these five cancerous tissues which can be considered the direct cofactors of CML disease. By relative node degree, resolution, possible ligand, stoichiometry, Q-mean, and Z-score analysis we found 11 hubs proteins like SMAD3, GRB2, TP53, SMAD4, RB1, HDAC1, RAF1, ABL1, SHC1, TGFBR1, RELA which can be regarded for further drug target identification. ConclusionsOur proposed network analysis reflects on the gene set interaction pattern of disease signaling pathways of humans. The integrated multidrug computational and experimental approaches boost up to improve the novel drug target approach. Besides, such a trove can yield unprecedented insights to lead to an enhanced understanding of potential application both in drug target optimization and for drug dislodging.

bioinformatics↗