Data-driven insights into deletions of Mycobacterium tuberculosis complex chromosomal DR region using spoligoforests

Cagri Ozcaglar; Amina Shabbeer; Natalia Kurepina; Bulent Yener; Kristin P. Bennett

doi:10.1109/BIBM.2011.64

Data-driven insights into deletions of Mycobacterium tuberculosis complex chromosomal DR region using spoligoforests

Cagri Ozcaglar, Amina Shabbeer, Natalia Kurepina, Bulent Yener, Kristin P. Bennett

Center for Discovery and Innovation

Hackensack Meridian School of Medicine

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

Abstract

Biomarkers of Mycobacterium tuberculosis complex (MTBC) mutate over time. Among the biomarkers of MTBC, spacer oligonucleotide type (spoligotype) and Mycobacterium Interspersed Repetitive Unit (MIRU) patterns are commonly used to genotype clinical MTBC strains. In this study, we present an evolution model of spoligotype rearrangements using MIRU patterns to disambiguate the ancestors of spoligotypes, in a large patient dataset from the United States Centers for Disease Control and Prevention (CDC). Based on the contiguous deletion assumption and rare observation of convergent evolution, we first generate the most parsimonious forest of spoligotypes, called a spoligo forest, using three genetic distance measures. An analysis of topological attributes of the spoligo forest and number of variations at the direct repeat (DR) locus of each strain reveals interesting properties of deletions in the DR region. First, we compare our mutation model to existing mutation models of spoligotypes and find that our mutation model produces as many within-lineage mutation events as other models, with slightly higher segregation accuracy. Second, based on our mutation model, the number of descendant spoligotypes follows a power law distribution. Third, contrary to prior studies, the power law distribution does not plausibly fit to the mutation length frequency. Finally, the total number of mutation events at consecutive DR loci follows a bimodal distribution, which results in accumulation of shorter deletions in the DR region. The two modes are spacers 13 and 40, which are hotspots for chromosomal rearrangements. The change point in the bimodal distribution is spacer 34, which is absent in most MTBC strains. This bimodal separation results in accumulation of shorter deletions, which explains why a power law distribution is not a plausible fit to the mutation length frequency.

Original language	English
Title of host publication	Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011
Pages	75-82
Number of pages	8
DOIs	https://doi.org/10.1109/BIBM.2011.64
State	Published - 2011
Event	2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011 - Atlanta, GA, United States Duration: Nov 12 2011 → Nov 15 2011

Publication series

Name	Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011

Conference

Conference	2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011
Country/Territory	United States
City	Atlanta, GA
Period	11/12/11 → 11/15/11

ASJC Scopus subject areas

Biomedical Engineering
Health Informatics
Health Information Management

Keywords

DR locus
MIRU-VNTR
Mycobacterium tuberculosis complex
mutation
spoligotype
tuberculosis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1109/BIBM.2011.64

Cite this

Ozcaglar, C., Shabbeer, A., Kurepina, N., Yener, B., & Bennett, K. P. (2011). Data-driven insights into deletions of Mycobacterium tuberculosis complex chromosomal DR region using spoligoforests. In Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011 (pp. 75-82). Article 6120411 (Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011). https://doi.org/10.1109/BIBM.2011.64

Ozcaglar, Cagri ; Shabbeer, Amina ; Kurepina, Natalia et al. / Data-driven insights into deletions of Mycobacterium tuberculosis complex chromosomal DR region using spoligoforests. Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011. 2011. pp. 75-82 (Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011).

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title = "Data-driven insights into deletions of Mycobacterium tuberculosis complex chromosomal DR region using spoligoforests",

abstract = "Biomarkers of Mycobacterium tuberculosis complex (MTBC) mutate over time. Among the biomarkers of MTBC, spacer oligonucleotide type (spoligotype) and Mycobacterium Interspersed Repetitive Unit (MIRU) patterns are commonly used to genotype clinical MTBC strains. In this study, we present an evolution model of spoligotype rearrangements using MIRU patterns to disambiguate the ancestors of spoligotypes, in a large patient dataset from the United States Centers for Disease Control and Prevention (CDC). Based on the contiguous deletion assumption and rare observation of convergent evolution, we first generate the most parsimonious forest of spoligotypes, called a spoligo forest, using three genetic distance measures. An analysis of topological attributes of the spoligo forest and number of variations at the direct repeat (DR) locus of each strain reveals interesting properties of deletions in the DR region. First, we compare our mutation model to existing mutation models of spoligotypes and find that our mutation model produces as many within-lineage mutation events as other models, with slightly higher segregation accuracy. Second, based on our mutation model, the number of descendant spoligotypes follows a power law distribution. Third, contrary to prior studies, the power law distribution does not plausibly fit to the mutation length frequency. Finally, the total number of mutation events at consecutive DR loci follows a bimodal distribution, which results in accumulation of shorter deletions in the DR region. The two modes are spacers 13 and 40, which are hotspots for chromosomal rearrangements. The change point in the bimodal distribution is spacer 34, which is absent in most MTBC strains. This bimodal separation results in accumulation of shorter deletions, which explains why a power law distribution is not a plausible fit to the mutation length frequency.",

keywords = "DR locus, MIRU-VNTR, Mycobacterium tuberculosis complex, mutation, spoligotype, tuberculosis",

author = "Cagri Ozcaglar and Amina Shabbeer and Natalia Kurepina and Bulent Yener and Bennett, {Kristin P.}",

year = "2011",

doi = "10.1109/BIBM.2011.64",

language = "English",

isbn = "9780769545745",

series = "Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011",

pages = "75--82",

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note = "2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011 ; Conference date: 12-11-2011 Through 15-11-2011",

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Ozcaglar, C, Shabbeer, A, Kurepina, N, Yener, B & Bennett, KP 2011, Data-driven insights into deletions of Mycobacterium tuberculosis complex chromosomal DR region using spoligoforests. in Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011., 6120411, Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011, pp. 75-82, 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011, Atlanta, GA, United States, 11/12/11. https://doi.org/10.1109/BIBM.2011.64

Data-driven insights into deletions of Mycobacterium tuberculosis complex chromosomal DR region using spoligoforests. / Ozcaglar, Cagri; Shabbeer, Amina; Kurepina, Natalia et al.
Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011. 2011. p. 75-82 6120411 (Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011).

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

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T1 - Data-driven insights into deletions of Mycobacterium tuberculosis complex chromosomal DR region using spoligoforests

AU - Ozcaglar, Cagri

AU - Shabbeer, Amina

AU - Kurepina, Natalia

AU - Yener, Bulent

AU - Bennett, Kristin P.

PY - 2011

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N2 - Biomarkers of Mycobacterium tuberculosis complex (MTBC) mutate over time. Among the biomarkers of MTBC, spacer oligonucleotide type (spoligotype) and Mycobacterium Interspersed Repetitive Unit (MIRU) patterns are commonly used to genotype clinical MTBC strains. In this study, we present an evolution model of spoligotype rearrangements using MIRU patterns to disambiguate the ancestors of spoligotypes, in a large patient dataset from the United States Centers for Disease Control and Prevention (CDC). Based on the contiguous deletion assumption and rare observation of convergent evolution, we first generate the most parsimonious forest of spoligotypes, called a spoligo forest, using three genetic distance measures. An analysis of topological attributes of the spoligo forest and number of variations at the direct repeat (DR) locus of each strain reveals interesting properties of deletions in the DR region. First, we compare our mutation model to existing mutation models of spoligotypes and find that our mutation model produces as many within-lineage mutation events as other models, with slightly higher segregation accuracy. Second, based on our mutation model, the number of descendant spoligotypes follows a power law distribution. Third, contrary to prior studies, the power law distribution does not plausibly fit to the mutation length frequency. Finally, the total number of mutation events at consecutive DR loci follows a bimodal distribution, which results in accumulation of shorter deletions in the DR region. The two modes are spacers 13 and 40, which are hotspots for chromosomal rearrangements. The change point in the bimodal distribution is spacer 34, which is absent in most MTBC strains. This bimodal separation results in accumulation of shorter deletions, which explains why a power law distribution is not a plausible fit to the mutation length frequency.

AB - Biomarkers of Mycobacterium tuberculosis complex (MTBC) mutate over time. Among the biomarkers of MTBC, spacer oligonucleotide type (spoligotype) and Mycobacterium Interspersed Repetitive Unit (MIRU) patterns are commonly used to genotype clinical MTBC strains. In this study, we present an evolution model of spoligotype rearrangements using MIRU patterns to disambiguate the ancestors of spoligotypes, in a large patient dataset from the United States Centers for Disease Control and Prevention (CDC). Based on the contiguous deletion assumption and rare observation of convergent evolution, we first generate the most parsimonious forest of spoligotypes, called a spoligo forest, using three genetic distance measures. An analysis of topological attributes of the spoligo forest and number of variations at the direct repeat (DR) locus of each strain reveals interesting properties of deletions in the DR region. First, we compare our mutation model to existing mutation models of spoligotypes and find that our mutation model produces as many within-lineage mutation events as other models, with slightly higher segregation accuracy. Second, based on our mutation model, the number of descendant spoligotypes follows a power law distribution. Third, contrary to prior studies, the power law distribution does not plausibly fit to the mutation length frequency. Finally, the total number of mutation events at consecutive DR loci follows a bimodal distribution, which results in accumulation of shorter deletions in the DR region. The two modes are spacers 13 and 40, which are hotspots for chromosomal rearrangements. The change point in the bimodal distribution is spacer 34, which is absent in most MTBC strains. This bimodal separation results in accumulation of shorter deletions, which explains why a power law distribution is not a plausible fit to the mutation length frequency.

KW - DR locus

KW - MIRU-VNTR

KW - Mycobacterium tuberculosis complex

KW - mutation

KW - spoligotype

KW - tuberculosis

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T3 - Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011

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BT - Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011

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Ozcaglar C, Shabbeer A, Kurepina N, Yener B, Bennett KP. Data-driven insights into deletions of Mycobacterium tuberculosis complex chromosomal DR region using spoligoforests. In Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011. 2011. p. 75-82. 6120411. (Proceedings - 2011 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2011). doi: 10.1109/BIBM.2011.64

Data-driven insights into deletions of Mycobacterium tuberculosis complex chromosomal DR region using spoligoforests

Abstract

Publication series

Conference

ASJC Scopus subject areas

Keywords

UN SDGs

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