Publications by authors named "N Kathiresan"

25 Publications

DeepSVP: Integration of genotype and phenotype for structural variant prioritization using deep learning.

Bioinformatics 2021 Dec 24. Epub 2021 Dec 24.

Computational Bioscience Research Center (CBRC), Computer, Electrical and Mathematical Sciences & Engineering Division (CEMSE), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia.

Motivation: Structural genomic variants account for much of human variability and are involved in several diseases. Structural variants are complex and may affect coding regions of multiple genes, or affect the functions of genomic regions in different ways from single nucleotide variants. Interpreting the phenotypic consequences of structural variants relies on information about gene functions, haploinsufficiency or triplosensitivity, and other genomic features. Phenotype-based methods to identifying variants that are involved in genetic diseases combine molecular features with prior knowledge about the phenotypic consequences of altering gene functions. While phenotype-based methods have been applied successfully to single nucleotide variants as well as short insertions and deletions, the complexity of structural variants makes it more challenging to link them to phenotypes. Furthermore, structural variants can affect a large number of coding regions, and phenotype information may not be available for all of them.

Results: We developed DeepSVP, a computational method to prioritize structural variants involved in genetic diseases by combining genomic and gene functions information. We incorporate phenotypes linked to genes, functions of gene products, gene expression in individual celltypes, and anatomical sites of expression, and systematically relate them to their phenotypic consequences through ontologies and machine learning. DeepSVP significantly improves the success rate of finding causative variants in several benchmarks and can identify novel pathogenic structural variants in consanguineous families.

Availability: https://github.com/bio-ontology-research-group/DeepSVP.
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http://dx.doi.org/10.1093/bioinformatics/btab859DOI Listing
December 2021

Factors Predicting Nodal Metastasis in Penile Cancer: Analysis from a Tertiary Center.

Urol Int 2021 Nov 24:1-6. Epub 2021 Nov 24.

Department of Surgical Oncology, Cancer Institute (WIA), Chennai, India.

Introduction: Lymph node metastasis is an important prognostic marker in penile cancer. Identification of occult metastasis is by lymphadenectomy based on the histological features of primary tumor; however, this leads to unnecessary surgical morbidity in node negative patients.

Methods: A retrospective analysis of all surgically treated penile cancer patients managed at our institute from January 2011 to March 2014 was performed. Patient characteristics, histological factors, and lymph node involvement were identified. Logistic regression analysis was used to compute odds ratio (OR) in univariate and multivariate analysis.

Results: Ninety seven patients underwent surgical management at our institute during the abovementioned period. Grade III tumor, presence of lymphovascular invasion, tumor thickness >10 mm, perineural invasion (PNI) and Ki67 >50% were significantly associated with nodal metastasis. On multivariate analysis, only presence of PNI was found to be significant (OR: 6.82) (95% confidence interval: 1.72-27.03) (p = 0.006).

Conclusion: PNI is a strong independent predictor of occult lymph node metastasis in penile cancers. Its inclusion in stratification of clinically node negative patients will identify high-risk patients who will benefit from prophylactic lymphadenectomy.
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http://dx.doi.org/10.1159/000519918DOI Listing
November 2021

Nerve-Sparing Postchemotherapy Retroperitoneal Lymph Node Dissection (PC RPLND) for Nonseminomatous Germ Cell Tumour: Experience from a Tertiary Cancer Centre.

Indian J Surg Oncol 2021 Jun 25;12(2):374-377. Epub 2021 Mar 25.

Department of Medical Oncology, Cancer Institute (WIA), Adyar, Chennai, India.

Postchemotherapy RPLND remains an integral part of management of testicular tumours. Nerve-sparing techniques can minimize the ejaculatory dysfunction due to the procedure. We report our functional and oncological outcomes for nerve-sparing RPLND in postchemotherapy settings. We analysed data from all patients undergoing nerve-sparing PC RPLND from January 1990 to December 2013 at our institute. Antegrade ejaculation and fertility issues were determined by patient history. Nerve sparing was achieved in 30% of patients undergoing PC RPLND. Of the 33 patients who underwent nerve-sparing PC RPLND, 19 (57.8%) had antegrade ejaculation. The mean time to antegrade ejaculation was 6.8 months. After a median follow-up of 75.61 months, 5-year disease-free survival was 98%. Nerve-sparing RPLND can improve functional outcomes without increasing recurrence rates in post chemotherapy setting.
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http://dx.doi.org/10.1007/s13193-021-01313-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272781PMC
June 2021

Correction: An essential role for α4A-tubulin in platelet biogenesis.

Life Sci Alliance 2021 Aug 21;4(8). Epub 2021 Jun 21.

Université de Strasbourg, Institut National de la Santé et de la Recherche Médicale, Etablissement Français du Sang Grand Est, Unité Mixte de Recherche-S 1255, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France.

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http://dx.doi.org/10.26508/lsa.202101132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321679PMC
August 2021
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