Biology subjects

Neeraja M Krishnan

Publications and source records attributed to Neeraja M Krishnan.

3 recordsLinked to original sources

bioRxiv2015

Integrated analysis links TP53, NOTCH, SLC38A and 11p with survival in patients with oral tongue squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) are a heterogeneous group of cancers affecting multiple subsites, including oral cavity. Oral or anterior tongue tumors (OTSCC) are an aggressive group of squamous cell carcinomas, characterized by their early spread to lymph nodes and higher rate of regional failure compared to other oral cavity cancers. There is a rise in the incidence of oral tongue cancer among younger population (<50yrs); many of who lack the typical associated risk factors of alcohol and/or tobacco exposure. In order to carry out an ensemble learning and prediction method with multiple parameters classifying survival, we generated data, on somatic mutations in genes from exome sequencing, immediate upstream and downstream flanking nucleotides of the somatic mutations, DNA methylation, loss of heterozygosity (LOH), copy number variations (CNV), gene expression, significant pathways altered and Human Papilloma Virus (HPV) infection, from 50 OTSCC patients. Results of our analysis identified somatic mutations in NOTCH2 and/or TP53, and/or LOH in 11p to associate with better disease free survival in HPV positive patients (P = 0.0254) and not in HPV negative patients (P = 0.414). We validated the latter in patients without HPV infection from TCGA cohort (P = 0.369, N = 17 for TCGA_ OralTongue; P = 0.472, N = 67 for all TCGA_HNSCC patients). Integrated analysis, including pathways, linked survival with apoptosis and aberrant methylation in SLC38A8 (P = 0.0129).\n\nAuthor SummaryOral tongue squamous cell carcinomas (OTSCC) are a homogenous group of head and neck tumors characterized with aggressive behavior among younger patients. In this report, we have analysed genetic variants, expression and DNA methylation changes across 50 oral tongue primary tumors along with the Human Papilloma Virus (HPV) infection status in those tumors to identify factors associated with disease free survival. Our data identified somatic mutations in the genes NOTCH2, TP53 and LOH in 11p, to be significantly associated with better disease free survival in HPV positive patients (P = 0.0254), but not in HPV negative patients (P = 0.414). We validated the latter using patients without HPV infection from TCGA (P = 0.369, N = 17 for TCGA_OralTongue; P = 0.472, N = 67 for all TCGA_HNSCC patients). Integrated analysis linked survival with apoptosis and aberrant methylation in SLC38A8 (P = 0.0129).

Genomics↗

bioRxiv2015

An Improved Genome Assembly of Azadirachta indica A. Juss.

Neem (Azadirachta indica A. Juss.), an evergreen tree of the Meliaceae family, is known for its medicinal, cosmetic, pesticidal and insecticidal properties. We had previously sequenced and published the draft genome of the plant, using mainly short read sequencing data. In this report, we present an improved genome assembly generated using additional short reads from Illumina and long reads from Pacific Biosciences SMRT sequencer. We assembled short reads and error-corrected long reads using Platanus, an assembler designed to perform well for heterozygous genomes. The updated genome assembly (v2.0) yielded 3- and 3.5-fold increase in N50 and N75, respectively; 2.6-fold decrease in the total number of scaffolds; 1.25-fold increase in the number of valid transcriptome alignments; 13.4-fold less mis-assembly and 1.85-fold increase in the percentage repeat, over the earlier assembly (v1.0). The current assembly also maps better to the genes known to be involved in the terpenoid biosynthesis pathway. Together, the data represents an improved assembly of the A. indica genome.\n\nThe raw data described in this manuscript are submitted to the NCBI Short Read Archive under the accession numbers SRX1074131, SRX1074132, SRX1074133, and SRX1074134 (SRP013453).

Bioinformatics↗

bioRxiv2015

Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence

Oral tongue squamous cell carcinomas (OTSCC) are a homogenous group of tumors characterized by aggressive behavior, early spread to lymph nodes and a higher rate of regional failure. Additionally, the incidence of OTSCC among younger population (<50yrs) is on a rise; many of who lack the typical associated risk factors of alcohol and/or tobacco exposure. We present data on SNVs, indels, regions with LOH, and CNVs from fifty-paired oral tongue primary tumors and link the significant somatic variants with clinical parameters, epidemiological factors including HPV infection and tumor recurrence. Apart from the frequent somatic variants harbored in TP53, CASP8, RASA1, NOTCH and CDKN2A genes, significant amplifications and/or deletions were detected in chromosomes 6-9, and 11 in the tumors. Variants in CASP8 and CDKN2A were mutually exclusive. CDKN2A, P1K3CA, RASA1 and DMD variants were exclusively linked to smoking, chewing, HPV infection and tumor stage. We also performed whole-genome gene expression study that identified matrix metalloproteases to be highly expressed in tumors and linked pathways involving arachidonic acid and NF-{kappa}-B to habits and distant metastasis, respectively. Functional knockdown studies in cell lines demonstrated the role of CASP8 in HPV-negative OTSCC cell line. Finally, we identified a 38-gene minimal signature that predicts tumor recurrence using an ensemble machine learning method. Taken together, this study links molecular signatures to various clinical and epidemiological factors in a homogeneous tumor population with a relatively high HPV prevalence.

Genomics↗