HPV16-Genotyper: A Computational Tool for Risk-Assessment, Lineage Genotyping and Recombination Detection in HPV16 Sequences, Based on a Large-Scale Evolutionary Analysis

Previous analyses have identified certain but limited evidence of recombination among HPV16 genomes, in accordance with a general perception that DNA viruses do not frequently recombine. In this evolutionary/bioinformatics study we have analyzed more than 3600 publicly available complete and partial...

Full description

Bibliographic Details
Main Authors: Marios Nikolaidis, Dimitris Tsakogiannis, Garyfalia Bletsa, Dimitris Mossialos, Christine Kottaridi, Ioannis Iliopoulos, Panayotis Markoulatos, Grigoris D. Amoutzias
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Diversity
Subjects:
Online Access:https://www.mdpi.com/1424-2818/13/10/497
_version_ 1797514823828766720
author Marios Nikolaidis
Dimitris Tsakogiannis
Garyfalia Bletsa
Dimitris Mossialos
Christine Kottaridi
Ioannis Iliopoulos
Panayotis Markoulatos
Grigoris D. Amoutzias
author_facet Marios Nikolaidis
Dimitris Tsakogiannis
Garyfalia Bletsa
Dimitris Mossialos
Christine Kottaridi
Ioannis Iliopoulos
Panayotis Markoulatos
Grigoris D. Amoutzias
author_sort Marios Nikolaidis
collection DOAJ
description Previous analyses have identified certain but limited evidence of recombination among HPV16 genomes, in accordance with a general perception that DNA viruses do not frequently recombine. In this evolutionary/bioinformatics study we have analyzed more than 3600 publicly available complete and partial HPV16 genomes. By studying the phylogenetic incongruence, similarity plots and the distribution patterns of lineage-specific SNPs, we identify several potential recombination events between the two major HPV16 evolutionary clades. These two clades comprise the (widely considered) phenotypically more benign (lower risk) lineage A and the (widely considered) phenotypically more aggressive (higher risk) non-European lineages B, C and D. We observe a frequency of potential recombinant sequences ranging between 0.3 and 1.2% which is low, but nevertheless considerable. Our findings have clinical implications and highlight that HPV16 genotyping and risk assessment based only on certain genomic regions and not the entire genome may provide a false genotype and, therefore, its associated risk estimate. Finally, based on this analysis, we have developed a bioinformatics tool that automates the entire process of HPV16 lineage genotyping, recombination detection and further identifies, within the submitted sequences, SNPs that have been reported in the literature to increase the risk of cancer.
first_indexed 2024-03-10T06:37:02Z
format Article
id doaj.art-d7043e9f61bf48cabd1c835a6146f82c
institution Directory Open Access Journal
issn 1424-2818
language English
last_indexed 2024-03-10T06:37:02Z
publishDate 2021-10-01
publisher MDPI AG
record_format Article
series Diversity
spelling doaj.art-d7043e9f61bf48cabd1c835a6146f82c2023-11-22T17:59:46ZengMDPI AGDiversity1424-28182021-10-01131049710.3390/d13100497HPV16-Genotyper: A Computational Tool for Risk-Assessment, Lineage Genotyping and Recombination Detection in HPV16 Sequences, Based on a Large-Scale Evolutionary AnalysisMarios Nikolaidis0Dimitris Tsakogiannis1Garyfalia Bletsa2Dimitris Mossialos3Christine Kottaridi4Ioannis Iliopoulos5Panayotis Markoulatos6Grigoris D. Amoutzias7Bioinformatics Laboratory, Department of Biochemistry and Biotechnology, University of Thessaly, 41500 Larissa, GreeceResearch Center, Hellenic Anticancer Institute, 10680 Athens, GreeceResearch Center, Hellenic Anticancer Institute, 10680 Athens, GreeceMicrobial Biotechnology-Molecular Bacteriology-Virology Laboratory, Department of Biochemistry and Biotechnology, University of Thessaly, 41500 Larissa, GreeceMicrobiology Laboratory, Department of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceSchool of Medicine, University of Crete, 71003 Heraklion, GreeceMicrobial Biotechnology-Molecular Bacteriology-Virology Laboratory, Department of Biochemistry and Biotechnology, University of Thessaly, 41500 Larissa, GreeceBioinformatics Laboratory, Department of Biochemistry and Biotechnology, University of Thessaly, 41500 Larissa, GreecePrevious analyses have identified certain but limited evidence of recombination among HPV16 genomes, in accordance with a general perception that DNA viruses do not frequently recombine. In this evolutionary/bioinformatics study we have analyzed more than 3600 publicly available complete and partial HPV16 genomes. By studying the phylogenetic incongruence, similarity plots and the distribution patterns of lineage-specific SNPs, we identify several potential recombination events between the two major HPV16 evolutionary clades. These two clades comprise the (widely considered) phenotypically more benign (lower risk) lineage A and the (widely considered) phenotypically more aggressive (higher risk) non-European lineages B, C and D. We observe a frequency of potential recombinant sequences ranging between 0.3 and 1.2% which is low, but nevertheless considerable. Our findings have clinical implications and highlight that HPV16 genotyping and risk assessment based only on certain genomic regions and not the entire genome may provide a false genotype and, therefore, its associated risk estimate. Finally, based on this analysis, we have developed a bioinformatics tool that automates the entire process of HPV16 lineage genotyping, recombination detection and further identifies, within the submitted sequences, SNPs that have been reported in the literature to increase the risk of cancer.https://www.mdpi.com/1424-2818/13/10/497HPV16evolutionphylogeneticsbioinformatics toolcancer riskSNPs
spellingShingle Marios Nikolaidis
Dimitris Tsakogiannis
Garyfalia Bletsa
Dimitris Mossialos
Christine Kottaridi
Ioannis Iliopoulos
Panayotis Markoulatos
Grigoris D. Amoutzias
HPV16-Genotyper: A Computational Tool for Risk-Assessment, Lineage Genotyping and Recombination Detection in HPV16 Sequences, Based on a Large-Scale Evolutionary Analysis
Diversity
HPV16
evolution
phylogenetics
bioinformatics tool
cancer risk
SNPs
title HPV16-Genotyper: A Computational Tool for Risk-Assessment, Lineage Genotyping and Recombination Detection in HPV16 Sequences, Based on a Large-Scale Evolutionary Analysis
title_full HPV16-Genotyper: A Computational Tool for Risk-Assessment, Lineage Genotyping and Recombination Detection in HPV16 Sequences, Based on a Large-Scale Evolutionary Analysis
title_fullStr HPV16-Genotyper: A Computational Tool for Risk-Assessment, Lineage Genotyping and Recombination Detection in HPV16 Sequences, Based on a Large-Scale Evolutionary Analysis
title_full_unstemmed HPV16-Genotyper: A Computational Tool for Risk-Assessment, Lineage Genotyping and Recombination Detection in HPV16 Sequences, Based on a Large-Scale Evolutionary Analysis
title_short HPV16-Genotyper: A Computational Tool for Risk-Assessment, Lineage Genotyping and Recombination Detection in HPV16 Sequences, Based on a Large-Scale Evolutionary Analysis
title_sort hpv16 genotyper a computational tool for risk assessment lineage genotyping and recombination detection in hpv16 sequences based on a large scale evolutionary analysis
topic HPV16
evolution
phylogenetics
bioinformatics tool
cancer risk
SNPs
url https://www.mdpi.com/1424-2818/13/10/497
work_keys_str_mv AT mariosnikolaidis hpv16genotyperacomputationaltoolforriskassessmentlineagegenotypingandrecombinationdetectioninhpv16sequencesbasedonalargescaleevolutionaryanalysis
AT dimitristsakogiannis hpv16genotyperacomputationaltoolforriskassessmentlineagegenotypingandrecombinationdetectioninhpv16sequencesbasedonalargescaleevolutionaryanalysis
AT garyfaliabletsa hpv16genotyperacomputationaltoolforriskassessmentlineagegenotypingandrecombinationdetectioninhpv16sequencesbasedonalargescaleevolutionaryanalysis
AT dimitrismossialos hpv16genotyperacomputationaltoolforriskassessmentlineagegenotypingandrecombinationdetectioninhpv16sequencesbasedonalargescaleevolutionaryanalysis
AT christinekottaridi hpv16genotyperacomputationaltoolforriskassessmentlineagegenotypingandrecombinationdetectioninhpv16sequencesbasedonalargescaleevolutionaryanalysis
AT ioannisiliopoulos hpv16genotyperacomputationaltoolforriskassessmentlineagegenotypingandrecombinationdetectioninhpv16sequencesbasedonalargescaleevolutionaryanalysis
AT panayotismarkoulatos hpv16genotyperacomputationaltoolforriskassessmentlineagegenotypingandrecombinationdetectioninhpv16sequencesbasedonalargescaleevolutionaryanalysis
AT grigorisdamoutzias hpv16genotyperacomputationaltoolforriskassessmentlineagegenotypingandrecombinationdetectioninhpv16sequencesbasedonalargescaleevolutionaryanalysis