Facilitated sequence counting and assembly by template mutagenesis

Levy, D., Wigler, M. (2014) Facilitated sequence counting and assembly by template mutagenesis. Proceedings of the National Academy of Sciences of the United States of America, 111 (43). E4632-E4637. ISSN 0027-8424

URL: http://www.ncbi.nlm.nih.gov/pubmed/25313059
DOI: 10.1073/pnas.1416204111

Abstract

Presently, inferring the long-range structure of the DNA templates is limited by short read lengths. Accurate template counts suffer from distortions occurring during PCR amplification. We explore the utility of introducing random mutations in identical or nearly identical templates to create distinguishable patterns that are inherited during subsequent copying. We simulate the applications of this process under assumptions of error-free sequencing and perfect mapping, using cytosine deamination as a model for mutation. The simulations demonstrate that within readily achievable conditions of nucleotide conversion and sequence coverage, we can accurately count the number of otherwise identical molecules as well as connect variants separated by long spans of identical sequence. We discuss many potential applications, such as transcript profiling, isoform assembly, haplotype phasing, and de novo genome assembly.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > annotation > gene expression profiling annotation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > copy number variants
CSHL Authors:
Communities: CSHL labs > Levy lab
CSHL labs > Wigler lab
CSHL Cancer Center Program > Cancer Genetics
Depositing User: Matt Covey
Date Deposited: 24 Oct 2014 14:57
Last Modified: 14 Oct 2015 19:13
PMCID: PMC4217440
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30870

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