A Pilot Study on the Whole Exome Sequencing of Prostate Cancer in the Indian Phenotype Reveals Distinct Polymorphisms

Gupta, Ayam; Shukla, Nidhi; Nehra, Mamta; Gupta, Sonal; Malik, Babita; Mishra, Ashwani Kumar; Vijay, Maneesh Kumar; Batra, Jyotsna; Lohiya, N. K.; Sharma, Devendra Kumar; Suravajhala, Prashanth

doi:10.3389/fgene.2020.00874

Cited by 12 publications

(8 citation statements)

References 40 publications

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“…Expression of COL6A1 is significantly elevated in different tumors such as lung, prostate, cervical and pancreatic cancer compared to normal tissues. Interestingly, our previous WES studies in PCa have identified COL6A1 as one of the causal genes [7], whereas, we also identified this through our RNA-seq analysis. COL6A1 was shown to be physically interacting with DNAJB11, APP along with some other genes.…”

Section: Discussionmentioning

confidence: 78%

“…Although studies have dealt with the genetics, genomics, and the environmental influence in causal of PCa, no association of genotype and phenotype employing the NGS approaches has been discussed in the Indian population. Recent studies from our lab using the whole-exome sequencing (WES) approach of PCa in India have yielded very promising results to identify causal genes specific to PCa with 30 causal genes to the Indian cohort and over 8 genes specific to Indian phenotype with variable degree of genetic disposition [7]. Whole transcriptome shotgun sequencing (WTSS) or RNA-sequencing (RNA-Seq) on the other hand is used to study regulation, developmental biology, clinical and health sector [8].…”

Section: Introductionmentioning

confidence: 99%

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Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort

Shukla¹,

Kour²,

Sharma³

et al. 2023

Preprint

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Prostate cancer (PCa) is one of the most prevalent cancers among men in India. Although studies on PCa have dealt with the genetics, genomics, and the environmental influence in causality of PCa, not many studies employing the next generation sequencing (NGS) approaches of PCa have been carried out. In our previous study, we have identified some causal genes and mutations specific to Indian PCa using Whole-Exome Sequencing (WES). In the recent past, with the help of different cancer consortiums such as The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), along with differentially expressed genes (DEGs), many cancer-associated novel non-coding RNAs have been identified as biomarkers. In this work, we attempt to identify DEGs as well as long non-coding RNAs (lncRNAs) associated with signature pathways from an Indian PCa cohort using RNA-sequencing (RNA-seq) approach. From a cohort of 60, we screened 6 patients who underwent prostatectomy; we performed a whole transcriptome shotgun sequencing (WTSS)/RNA-sequencing to decipher the DEGs. We further normalized the read counts using fragments per kilobase of transcript per million mapped reads (FPKM) and analyzed the DEGs using a cohort of downstream regulatory tools, viz. GeneMANIA Stringdb, Cytoscape-Cytohubba, cbioportal to map the inherent signatures associated with PCa. By comparing the RNA-seq data obtained from the pairs of normal and PCa tissue samples using our benchmarked in-house cuffdiff pipeline, we observed some important genes specific to PCa such as STEAP2, APP, PMEPA1, PABPC1, NFE2L2, HN1L and some other important genes known to be involved in different cancer pathways such as, COL6A1, DOK5, STX6, BCAS1, BACE1, BACE2, LMOD1, SNX9, CTNND1 etc. We also identified a few novel lncRNAs such as LINC01440, SOX2OT, ENSG00000232855, and ENST00000647843.1 that need to be characterized further. Deregulation of SOX2OT is observed in various tumors, including lung cancer, gastric cancer, esophageal cancer, breast cancer, hepatocellular carcinoma, ovarian cancer, pancreatic, laryngeal squamous cell carcinoma, osteosarcoma, nasopharyngeal carcinoma, and glioblastoma. It would be interesting to characterize its function in PCa as well. In comparison with publicly available datasets, we have identified characteristic DEGs and novel lncRNAs implicated in signature PCa pathways in an Indian PCa cohort which have perhaps not been reported. As a pilot study, this has set a precedent for us to validate further experimentally, and we firmly believe this will pave a way towards discovery of biomarkers and development of novel therapies.

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort

Shukla¹,

Kour²,

Sharma³

et al. 2023

Preprint

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“…Only TNNI3, CTXN1, SLC27A5, HSPA12B , and ENSSSCG00000032730 presented increased RNA levels in P in at least three of the four samples ( Supplementary Table 4 ). According to the GTEx portal (dbGaP accession number phs000424.v8.ps ), TNNI3 , a component of the striated muscle filaments, is exclusively expressed in the heart although one study linked it to prostate cancer ( 30 ). CTXN1 is most highly expressed in the brain but it is also present at lower levels in several other tissues including testis, and its function is related to brain biology ( 31 ).…”

Section: Resultsmentioning

confidence: 99%

Characterization of the Impact of Density Gradient Centrifugation on the Profile of the Pig Sperm Transcriptome by RNA-Seq

Gòdia

Castelló

et al. 2021

Front. Vet. Sci.

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RNA-Seq data from human semen suggests that the study of the sperm transcriptome requires the previous elimination from the ejaculates of somatic cells carrying a larger load of RNA. Semen purification is also carried to study the sperm transcriptome in other species including swine and it is often done by density gradient centrifugation to obtain viable spermatozoa from fresh ejaculates or artificial insemination doses, thereby limiting the throughput and remoteness of the samples that can be processed in one study. The aim of this work was to evaluate the impact of purification with density gradient centrifugation by BoviPureTM on porcine sperm. Four boar ejaculates were purified with BoviPureTM and their transcriptome sequenced by RNA-Seq was compared with the RNA-Seq profiles of their paired non-purified sample. Seven thousand five hundred and nineteen protein coding genes were identified. Correlation, cluster, and principal component analysis indicated high—although not complete—similarity between the purified and the paired non-purified ejaculates. 372 genes displayed differentially abundant RNA levels between treatments. Most of these genes had lower abundances after purification and were mostly related to translation, transcription and metabolic processes. We detected a significant change in the proportion of genes of epididymal origin within the differentially abundant genes (1.3%) when compared with the catalog of unaltered genes (0.2%). In contrast, the proportion of testis-specific genes was higher in the group of unaltered genes (4%) when compared to the list of differentially abundant genes (0%). No proportion differences were identified for prostate, white blood, lymph node, tonsil, duodenum, skeletal muscle, liver, and mammary gland. Altogether, these results suggest that the purification impacts on the RNA levels of a small number of genes which are most likely caused by the removal of epididymal epithelial cells but also premature germinal cells, immature or abnormal spermatozoa or seminal exosomes with a distinct load of RNAs.

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“…In this work, we performed a trio exome analysis with the use of two trio pipelines, viz . VarScan Trio and GATK joint calling pipelines on Congenital Pouch Colon (CPC) samples from our rare disease cohort (Mathur et al, 2018, Gupta et al 2021, Gupta et al 2022) and Prostate cancer (PCa) (Gupta et al 2020) which we have published earlier. We attempted to compare the benchmarking results by analysing four datasets with a high confidence variant call set by the Genome in a Bottle (GIAB) consortium besides considering a truth set for pipeline performance validation to confirm their association with disease-causing mutations in CPC and PCa.…”

Section: Introductionmentioning

confidence: 99%

Benchmarking whole exome sequencing pipeline for predicting pathogenic variants of significance

Raju,

Singh,

Suravajhala

2023

Preprint

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Benchmarking whole exome pipelines is crucial for evaluating and comparing their performance in variant calling and clinical significance annotation. It enables researchers and clinicians to assess the accuracy, sensitivity, and specificity of different pipelines and identify the most effective and reliable ones. In this study, we evaluated and compared the performance of our in-house consensus exome pipeline with a widely recognized gold standard Genome Analysis Toolkit (GATK) pipeline. Four datasets were used for evaluation, three 1000 Genome Project (1KGP) datasets and one Prostate cancer (PCa) Sample. The consensus pipeline consistently demonstrated a higher average transition-to-transversion (Ti/Tv) ratio, indicating enhanced precision in identifying single nucleotide variant (SNV) calls. This suggests that the consensus pipeline excels in effectively discerning true genetic variations from sequencing artefacts, particularly in the context of exome sequencing. Additionally, the pipeline exhibited increased sensitivity in detecting pathogenic and likely pathogenic variants in the PCa sample, further highlighting its efficacy in identifying clinically relevant variants. We also conducted a trio exome analysis with the use of two trio pipelines,viz. VarScan Trio and GATK joint calling pipelines on our erstwhile Congenital Pouch Colon (CPC) samples from our rare disease cohort which we published earlier and found that the GATK predicted a significantly higher number of variants compared to VarScan. Our study demonstrates a large potential for trio-variant calling analysis paving the way for precision medicine.

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A Pilot Study on the Whole Exome Sequencing of Prostate Cancer in the Indian Phenotype Reveals Distinct Polymorphisms

Cited by 12 publications

References 40 publications

Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort

Towards Understanding the Key Signature Pathways Associated from Differentially Expressed Gene Analysis in an Indian Prostate Cancer Cohort

Characterization of the Impact of Density Gradient Centrifugation on the Profile of the Pig Sperm Transcriptome by RNA-Seq

Benchmarking whole exome sequencing pipeline for predicting pathogenic variants of significance

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