PMID- 22343484
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211021
IS  - 2156-1125 (Print)
IS  - 2156-1125 (Linking)
DP  - 2011
TI  - Data-driven insights into deletions of Mycobacterium tuberculosis complex 
      chromosomal DR region using spoligoforests.
PG  - 75-82
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 spoligoforest, using three genetic 
      distance measures. An analysis of topological attributes of the spoligoforest 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.
FAU - Ozcaglar, Cagri
AU  - Ozcaglar C
AD  - Computer Science Department, Rensselaer Polytechnic Institute, Troy, NY.
FAU - Shabbeer, Amina
AU  - Shabbeer A
FAU - Kurepina, Natalia
AU  - Kurepina N
FAU - Yener, Bulent
AU  - Yener B
FAU - Bennett, Kristin P
AU  - Bennett KP
LA  - eng
GR  - R01 LM009731/LM/NLM NIH HHS/United States
GR  - R01 LM009731-04/LM/NLM NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Proceedings (IEEE Int Conf Bioinformatics Biomed)
JT  - Proceedings. IEEE International Conference on Bioinformatics and Biomedicine
JID - 101525347
PMC - PMC3279189
MID - NIHMS352812
EDAT- 2012/02/22 06:00
MHDA- 2012/02/22 06:01
PMCR- 2012/02/14
CRDT- 2012/02/21 06:00
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/02/22 06:01 [medline]
PHST- 2012/02/14 00:00 [pmc-release]
AID - 10.1109/BIBM.2011.64 [doi]
PST - ppublish
SO  - Proceedings (IEEE Int Conf Bioinformatics Biomed). 2011:75-82. doi: 
      10.1109/BIBM.2011.64.