ABSTRACT
MOTIVATION: The detection of genomic regions unusually rich in a given pattern is an important undertaking in the analysis of next-generation sequencing data. Recent studies of chromosomal translocations in activated B lymphocytes have identified regions that are frequently translocated to c-myc oncogene. A quantitative method for the identification of translocation hotspots was crucial to this study. Here we improve this analysis by using a simple probabilistic model and the framework provided by scan statistics to define the number and location of translocation breakpoint hotspots. A key feature of our method is that it provides a global chromosome-wide nominal control level to clustering, as opposed to previous methods based on local criteria. While being motivated by a specific application, the detection of unusual clusters is a widespread problem in bioinformatics. We expect our method to be useful in the analysis of data from other experimental approaches such as of ChIP-seq and 4C-seq. RESULTS: The analysis of translocations from B lymphocytes with the method described here reveals the presence of longer hotspots when compared with those defined previously. Further, we show that the hotspot size changes substantially in the absence of DNA repair protein 53BP1. When 53BP1 deficiency is combined with overexpression of activation-induced cytidine deaminase, the hotspot length increases even further. These changes are not detected by previous methods that use local significance criteria for clustering. Our method is also able to identify several exclusive translocation hotspots located in genes of known tumor supressors. AVAILABILITY AND IMPLEMENTATION: The detection of translocation hotspots is done with hot_scan, a program implemented in R and Perl. Source code and documentation are freely available for download at https://github.com/itojal/hot_scan.
Subject(s)
Biometry/methods , Genomics/methods , Translocation, Genetic/genetics , B-Lymphocytes/metabolism , Chromosome Breakpoints , Cluster Analysis , Cytidine Deaminase/genetics , DNA Repair , High-Throughput Nucleotide Sequencing , Models, StatisticalABSTRACT
There is general agreement that the Native American founder populations migrated from Asia into America through Beringia sometime during the Pleistocene, but the hypotheses concerning the ages and the number of these migrations and the size of the ancestral populations are surrounded by controversy. DNA sequence variations of several regions of the genome of Native Americans, especially in the mitochondrial DNA (mtDNA) control region, have been studied as a tool to help answer these questions. However, the small number of nucleotides studied and the nonclocklike rate of mtDNA control-region evolution impose several limitations to these results. Here we provide the sequence analysis of a continuous region of 8.8 kb of the mtDNA outside the D-loop for 40 individuals, 30 of whom are Native Americans whose mtDNA belongs to the four founder haplogroups. Haplogroups A, B, and C form monophyletic clades, but the five haplogroup D sequences have unstable positions and usually do not group together. The high degree of similarity in the nucleotide diversity and time of differentiation (i.e., approximately 21,000 years before present) of these four haplogroups support a common origin for these sequences and suggest that the populations who harbor them may also have a common history. Additional evidence supports the idea that this age of differentiation coincides with the process of colonization of the New World and supports the hypothesis of a single and early entry of the ancestral Asian population into the Americas.
Subject(s)
DNA, Mitochondrial/genetics , Emigration and Immigration/history , Founder Effect , Indians, North American/genetics , Base Sequence , DNA, Mitochondrial/history , Evolution, Molecular , Genetic Variation , Genetics, Population/history , History, Ancient , Humans , Indians, North American/history , Models, Genetic , Molecular Sequence DataABSTRACT
Foi estudada a relação entre as propriedades mecânicas de fêmures de coelhos adultos jovens obtidas nos ensaios de flexão em três pontos e impacto, e a orientação das fibras de colágeno, bem como a energia absorvida nos dois ensaios. O ensaio de flexão em três pontos foi realizado nos 20 fêmures esquerdos para obtenção das seguintes propriedades: limite máximo, limite proporcional, rigidez, resiliência e tenacidade. O ensaio de impacto foi realizado nos 20 fêmures direitos para obtenção da energia absorvida no impacto. A orientação das fibras de colágeno de secções próximas às fraturas dos fêmures ensaiados foi estimada utilizando a técnica de polarização da luz. A análise de regressão mostrou que, na flexão, a rigidez teve correlação positiva (r = 0,43) e a resiliência, correlação negativa (r = -0,46) com a orientação das fibras de colágeno. A tenacidade no impacto não apresentou índice de correlação significante (p < 0,05). A energia absorvida pelos fêmures no ensaio de impacto foi 4,73 vezes a energia absorvida no ensaio de flexão em três pontos.
Subject(s)
Animals , Rabbits , Bone and Bones , Collagen , Biomechanical PhenomenaABSTRACT
A investigação deste estudo teve por objetivo analisar o efeito do ultrasom terapêutico em lesões musculares. Foi realizada análise biomecânica através de ensaios de tração dos músculos. Os resultados obtidos neste trabalho sugerem que a estimulação com ultrasom fisioterápico acelera o processo cicatricial no tipo de lesão proposto.
The proposal of this study was to analyse the therapeutic ultrasound effect in muscle injuries. Mechanical assays were carried out done to permit biomechanical analyses. The results suggest that the therapeutic ultrasound stimulation increase the healing process of this rind of injuries.
