Cargando…
InPhaDel: integrative shotgun and proximity-ligation sequencing to phase deletions with single nucleotide polymorphisms
Phasing of single nucleotide (SNV), and structural variations into chromosome-wide haplotypes in humans has been challenging, and required either trio sequencing or restricting phasing to population-based haplotypes. Selvaraj et al. demonstrated single individual SNV phasing is possible with proximi...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937317/ https://www.ncbi.nlm.nih.gov/pubmed/27105843 http://dx.doi.org/10.1093/nar/gkw281 |
_version_ | 1782441690150207488 |
---|---|
author | Patel, Anand Edge, Peter Selvaraj, Siddarth Bansal, Vikas Bafna, Vineet |
author_facet | Patel, Anand Edge, Peter Selvaraj, Siddarth Bansal, Vikas Bafna, Vineet |
author_sort | Patel, Anand |
collection | PubMed |
description | Phasing of single nucleotide (SNV), and structural variations into chromosome-wide haplotypes in humans has been challenging, and required either trio sequencing or restricting phasing to population-based haplotypes. Selvaraj et al. demonstrated single individual SNV phasing is possible with proximity ligated (HiC) sequencing. Here, we demonstrate HiC can phase structural variants into phased scaffolds of SNVs. Since HiC data is noisy, and SV calling is challenging, we applied a range of supervised classification techniques, including Support Vector Machines and Random Forest, to phase deletions. Our approach was demonstrated on deletion calls and phasings on the NA12878 human genome. We used three NA12878 chromosomes and simulated chromosomes to train model parameters. The remaining NA12878 chromosomes withheld from training were used to evaluate phasing accuracy. Random Forest had the highest accuracy and correctly phased 86% of the deletions with allele-specific read evidence. Allele-specific read evidence was found for 76% of the deletions. HiC provides significant read evidence for accurately phasing 33% of the deletions. Also, eight of eight top ranked deletions phased by only HiC were validated using long range polymerase chain reaction and Sanger. Thus, deletions from a single individual can be accurately phased using a combination of shotgun and proximity ligation sequencing. InPhaDel software is available at: http://l337x911.github.io/inphadel/. |
format | Online Article Text |
id | pubmed-4937317 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49373172016-07-11 InPhaDel: integrative shotgun and proximity-ligation sequencing to phase deletions with single nucleotide polymorphisms Patel, Anand Edge, Peter Selvaraj, Siddarth Bansal, Vikas Bafna, Vineet Nucleic Acids Res Methods Online Phasing of single nucleotide (SNV), and structural variations into chromosome-wide haplotypes in humans has been challenging, and required either trio sequencing or restricting phasing to population-based haplotypes. Selvaraj et al. demonstrated single individual SNV phasing is possible with proximity ligated (HiC) sequencing. Here, we demonstrate HiC can phase structural variants into phased scaffolds of SNVs. Since HiC data is noisy, and SV calling is challenging, we applied a range of supervised classification techniques, including Support Vector Machines and Random Forest, to phase deletions. Our approach was demonstrated on deletion calls and phasings on the NA12878 human genome. We used three NA12878 chromosomes and simulated chromosomes to train model parameters. The remaining NA12878 chromosomes withheld from training were used to evaluate phasing accuracy. Random Forest had the highest accuracy and correctly phased 86% of the deletions with allele-specific read evidence. Allele-specific read evidence was found for 76% of the deletions. HiC provides significant read evidence for accurately phasing 33% of the deletions. Also, eight of eight top ranked deletions phased by only HiC were validated using long range polymerase chain reaction and Sanger. Thus, deletions from a single individual can be accurately phased using a combination of shotgun and proximity ligation sequencing. InPhaDel software is available at: http://l337x911.github.io/inphadel/. Oxford University Press 2016-07-08 2016-04-21 /pmc/articles/PMC4937317/ /pubmed/27105843 http://dx.doi.org/10.1093/nar/gkw281 Text en Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US. |
spellingShingle | Methods Online Patel, Anand Edge, Peter Selvaraj, Siddarth Bansal, Vikas Bafna, Vineet InPhaDel: integrative shotgun and proximity-ligation sequencing to phase deletions with single nucleotide polymorphisms |
title | InPhaDel: integrative shotgun and proximity-ligation sequencing to phase deletions with single nucleotide polymorphisms |
title_full | InPhaDel: integrative shotgun and proximity-ligation sequencing to phase deletions with single nucleotide polymorphisms |
title_fullStr | InPhaDel: integrative shotgun and proximity-ligation sequencing to phase deletions with single nucleotide polymorphisms |
title_full_unstemmed | InPhaDel: integrative shotgun and proximity-ligation sequencing to phase deletions with single nucleotide polymorphisms |
title_short | InPhaDel: integrative shotgun and proximity-ligation sequencing to phase deletions with single nucleotide polymorphisms |
title_sort | inphadel: integrative shotgun and proximity-ligation sequencing to phase deletions with single nucleotide polymorphisms |
topic | Methods Online |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937317/ https://www.ncbi.nlm.nih.gov/pubmed/27105843 http://dx.doi.org/10.1093/nar/gkw281 |
work_keys_str_mv | AT patelanand inphadelintegrativeshotgunandproximityligationsequencingtophasedeletionswithsinglenucleotidepolymorphisms AT edgepeter inphadelintegrativeshotgunandproximityligationsequencingtophasedeletionswithsinglenucleotidepolymorphisms AT selvarajsiddarth inphadelintegrativeshotgunandproximityligationsequencingtophasedeletionswithsinglenucleotidepolymorphisms AT bansalvikas inphadelintegrativeshotgunandproximityligationsequencingtophasedeletionswithsinglenucleotidepolymorphisms AT bafnavineet inphadelintegrativeshotgunandproximityligationsequencingtophasedeletionswithsinglenucleotidepolymorphisms |