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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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Correlation between actual and estimated mean telomere lengths.S—single-end reads, P—paired-end reads. Estimation of mean telomere length was performed with reads generated from 200 kb length region of human chromosome 1, with telomeres attached to both its ends with lengths sampled from a normal distribution with mean 10 kb and SD 7 kb. The minimum-maximum range of the generated telomere lengths were: 194.5–21138 bp for single-end reads, and 387.5–24169.5 bp for paired-end reads. The read length, insert size and fold coverage ranges are described in the Materials and Methods.
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pone.0125201.g003: Correlation between actual and estimated mean telomere lengths.S—single-end reads, P—paired-end reads. Estimation of mean telomere length was performed with reads generated from 200 kb length region of human chromosome 1, with telomeres attached to both its ends with lengths sampled from a normal distribution with mean 10 kb and SD 7 kb. The minimum-maximum range of the generated telomere lengths were: 194.5–21138 bp for single-end reads, and 387.5–24169.5 bp for paired-end reads. The read length, insert size and fold coverage ranges are described in the Materials and Methods.

Mentions: The results obtained showed very strong linear correlation between actual and estimated telomere lengths in all the experiments, with the quality of linear fit (R2) equal to 0.95 and 0.92 for single and paired-end reads, respectively (Fig 3). The mean relative errors (MRE±SE) between estimated and actual telomere lengths were 4±0.01% for single-end reads and 7±0.01% for paired-end reads.


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

Nersisyan L, Arakelyan A - PLoS ONE (2015)

Correlation between actual and estimated mean telomere lengths.S—single-end reads, P—paired-end reads. Estimation of mean telomere length was performed with reads generated from 200 kb length region of human chromosome 1, with telomeres attached to both its ends with lengths sampled from a normal distribution with mean 10 kb and SD 7 kb. The minimum-maximum range of the generated telomere lengths were: 194.5–21138 bp for single-end reads, and 387.5–24169.5 bp for paired-end reads. The read length, insert size and fold coverage ranges are described in the Materials and Methods.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0125201.g003: Correlation between actual and estimated mean telomere lengths.S—single-end reads, P—paired-end reads. Estimation of mean telomere length was performed with reads generated from 200 kb length region of human chromosome 1, with telomeres attached to both its ends with lengths sampled from a normal distribution with mean 10 kb and SD 7 kb. The minimum-maximum range of the generated telomere lengths were: 194.5–21138 bp for single-end reads, and 387.5–24169.5 bp for paired-end reads. The read length, insert size and fold coverage ranges are described in the Materials and Methods.
Mentions: The results obtained showed very strong linear correlation between actual and estimated telomere lengths in all the experiments, with the quality of linear fit (R2) equal to 0.95 and 0.92 for single and paired-end reads, respectively (Fig 3). The mean relative errors (MRE±SE) between estimated and actual telomere lengths were 4±0.01% for single-end reads and 7±0.01% for paired-end reads.

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