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Computel: computation of mean telomere length from whole-genome next-generation sequencing data.

Nersisyan L, Arakelyan A - PLoS ONE (2015)

Bottom Line: We validated it with synthetic and experimental data, and compared its performance with the previously available software.The results have shown that Computel outperforms existing software in accuracy, independence of results from sequencing conditions, stability against inherent sequencing errors, and better ability to distinguish pure telomeric sequences from interstitial telomeric repeats.By providing a highly reliable methodology for determining telomere lengths from whole-genome sequencing data, Computel should help to elucidate the role of telomeres in cellular health and disease.

View Article: PubMed Central - PubMed

Affiliation: Group of Bioinformatics of the Institute of Molecular Biology of the National Academy of Sciences of the Republic of Armenia, Yerevan, Armenia.

ABSTRACT
Telomeres are the ends of eukaryotic chromosomes, consisting of consecutive short repeats that protect chromosome ends from degradation. Telomeres shorten with each cell division, leading to replicative cell senescence. Deregulation of telomere length homeostasis is associated with the development of various age-related diseases and cancers. A number of experimental techniques exist for telomere length measurement; however, until recently, the absence of tools for extracting telomere lengths from high-throughput sequencing data has significantly obscured the association of telomere length with molecular processes in normal and diseased conditions. We have developed Computel, a program in R for computing mean telomere length from whole-genome next-generation sequencing data. Computel is open source, and is freely available at https://github.com/lilit-nersisyan/computel. It utilizes a short-read alignment-based approach and integrates various popular tools for sequencing data analysis. We validated it with synthetic and experimental data, and compared its performance with the previously available software. The results have shown that Computel outperforms existing software in accuracy, independence of results from sequencing conditions, stability against inherent sequencing errors, and better ability to distinguish pure telomeric sequences from interstitial telomeric repeats. By providing a highly reliable methodology for determining telomere lengths from whole-genome sequencing data, Computel should help to elucidate the role of telomeres in cellular health and disease.

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Related in: MedlinePlus

Schematic representation of the Computel algorithm for mean telomere length estimation.Computel takes whole-genome NGS short-reads as input; maps them to the telomeric index built based on user-defined telomeric repeat pattern and the read length; and calculates the mean telomere length based on the ratio of telomeric and reference genome coverage, the number of chromosomes, and the read length.
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pone.0125201.g001: Schematic representation of the Computel algorithm for mean telomere length estimation.Computel takes whole-genome NGS short-reads as input; maps them to the telomeric index built based on user-defined telomeric repeat pattern and the read length; and calculates the mean telomere length based on the ratio of telomeric and reference genome coverage, the number of chromosomes, and the read length.

Mentions: The general workflow of mean telomere length estimation by Computel is schematically represented in Fig 1. It consists of the following steps: (1) building a telomeric index, (2) mapping reads to the telomeric index, (3) coverage calculation at the telomeric index, (4) determination of mean coverage at reference genome (optional), (5) estimation of mean telomere length. Each of these steps is described in detail in the following subsections.


Computel: computation of mean telomere length from whole-genome next-generation sequencing data.

Nersisyan L, Arakelyan A - PLoS ONE (2015)

Schematic representation of the Computel algorithm for mean telomere length estimation.Computel takes whole-genome NGS short-reads as input; maps them to the telomeric index built based on user-defined telomeric repeat pattern and the read length; and calculates the mean telomere length based on the ratio of telomeric and reference genome coverage, the number of chromosomes, and the read length.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414351&req=5

pone.0125201.g001: Schematic representation of the Computel algorithm for mean telomere length estimation.Computel takes whole-genome NGS short-reads as input; maps them to the telomeric index built based on user-defined telomeric repeat pattern and the read length; and calculates the mean telomere length based on the ratio of telomeric and reference genome coverage, the number of chromosomes, and the read length.
Mentions: The general workflow of mean telomere length estimation by Computel is schematically represented in Fig 1. It consists of the following steps: (1) building a telomeric index, (2) mapping reads to the telomeric index, (3) coverage calculation at the telomeric index, (4) determination of mean coverage at reference genome (optional), (5) estimation of mean telomere length. Each of these steps is described in detail in the following subsections.

Bottom Line: We validated it with synthetic and experimental data, and compared its performance with the previously available software.The results have shown that Computel outperforms existing software in accuracy, independence of results from sequencing conditions, stability against inherent sequencing errors, and better ability to distinguish pure telomeric sequences from interstitial telomeric repeats.By providing a highly reliable methodology for determining telomere lengths from whole-genome sequencing data, Computel should help to elucidate the role of telomeres in cellular health and disease.

View Article: PubMed Central - PubMed

Affiliation: Group of Bioinformatics of the Institute of Molecular Biology of the National Academy of Sciences of the Republic of Armenia, Yerevan, Armenia.

ABSTRACT
Telomeres are the ends of eukaryotic chromosomes, consisting of consecutive short repeats that protect chromosome ends from degradation. Telomeres shorten with each cell division, leading to replicative cell senescence. Deregulation of telomere length homeostasis is associated with the development of various age-related diseases and cancers. A number of experimental techniques exist for telomere length measurement; however, until recently, the absence of tools for extracting telomere lengths from high-throughput sequencing data has significantly obscured the association of telomere length with molecular processes in normal and diseased conditions. We have developed Computel, a program in R for computing mean telomere length from whole-genome next-generation sequencing data. Computel is open source, and is freely available at https://github.com/lilit-nersisyan/computel. It utilizes a short-read alignment-based approach and integrates various popular tools for sequencing data analysis. We validated it with synthetic and experimental data, and compared its performance with the previously available software. The results have shown that Computel outperforms existing software in accuracy, independence of results from sequencing conditions, stability against inherent sequencing errors, and better ability to distinguish pure telomeric sequences from interstitial telomeric repeats. By providing a highly reliable methodology for determining telomere lengths from whole-genome sequencing data, Computel should help to elucidate the role of telomeres in cellular health and disease.

Show MeSH
Related in: MedlinePlus