17,237 research outputs found
Reference genome and comparative genome analysis for the WHO reference strain for Mycobacterium bovis BCG Danish, the present tuberculosis vaccine
Background: Mycobacterium bovis bacillus Calmette-Guerin (M. bovis BCG) is the only vaccine available against tuberculosis (TB). In an effort to standardize the vaccine production, three substrains, i.e. BCG Danish 1331, Tokyo 172-1 and Russia BCG-1 were established as the WHO reference strains. Both for BCG Tokyo 172-1 as Russia BCG-1, reference genomes exist, not for BCG Danish. In this study, we set out to determine the completely assembled genome sequence for BCG Danish and to establish a workflow for genome characterization of engineering-derived vaccine candidate strains.ResultsBy combining second (Illumina) and third (PacBio) generation sequencing in an integrated genome analysis workflow for BCG, we could construct the completely assembled genome sequence of BCG Danish 1331 (07/270) (and an engineered derivative that is studied as an improved vaccine candidate, a SapM KO), including the resolution of the analytically challenging long duplication regions. We report the presence of a DU1-like duplication in BCG Danish 1331, while this tandem duplication was previously thought to be exclusively restricted to BCG Pasteur. Furthermore, comparative genome analyses of publicly available data for BCG substrains showed the absence of a DU1 in certain BCG Pasteur substrains and the presence of a DU1-like duplication in some BCG China substrains. By integrating publicly available data, we provide an update to the genome features of the commonly used BCG strains.
Conclusions: We demonstrate how this analysis workflow enables the resolution of genome duplications and of the genome of engineered derivatives of the BCG Danish vaccine strain. The BCG Danish WHO reference genome will serve as a reference for future engineered strains and the established workflow can be used to enhance BCG vaccine standardization
Graph Theory and Networks in Biology
In this paper, we present a survey of the use of graph theoretical techniques
in Biology. In particular, we discuss recent work on identifying and modelling
the structure of bio-molecular networks, as well as the application of
centrality measures to interaction networks and research on the hierarchical
structure of such networks and network motifs. Work on the link between
structural network properties and dynamics is also described, with emphasis on
synchronization and disease propagation.Comment: 52 pages, 5 figures, Survey Pape
A Running Time Improvement for Two Thresholds Two Divisors Algorithm
Chunking algorithms play an important role in data de-duplication systems. The Basic Sliding Window (BSW) algorithm is the first prototype of the content-based chunking algorithm which can handle most types of data. The Two Thresholds Two Divisors (TTTD) algorithm was proposed to improve the BSW algorithm in terms of controlling the variations of the chunk-size. In this project, we investigate and compare the BSW algorithm and TTTD algorithm from different factors by a series of systematic experiments. Up to now, no paper conducts these experimental evaluations for these two algorithms. This is the first value of this paper. According to our analyses and the results of experiments, we provide a running time improvement for the TTTD algorithm. Our new solution reduces about 7 % of the total running time and also reduces about 50 % of the large-sized chunks while comparing with the original TTTD algorithm and make average chunk-size closer to the expected chunk-size. These significant results are the second important value of this project
Characterization of duplicate gene evolution in the recent natural allopolyploid Tragopogon miscellus by next-generation sequencing and Sequenom iPLEX MassARRAY genotyping
The definitive version is available at www.blackwell-synergy.co
The inference of gene trees with species trees
Molecular phylogeny has focused mainly on improving models for the
reconstruction of gene trees based on sequence alignments. Yet, most
phylogeneticists seek to reveal the history of species. Although the histories
of genes and species are tightly linked, they are seldom identical, because
genes duplicate, are lost or horizontally transferred, and because alleles can
co-exist in populations for periods that may span several speciation events.
Building models describing the relationship between gene and species trees can
thus improve the reconstruction of gene trees when a species tree is known, and
vice-versa. Several approaches have been proposed to solve the problem in one
direction or the other, but in general neither gene trees nor species trees are
known. Only a few studies have attempted to jointly infer gene trees and
species trees. In this article we review the various models that have been used
to describe the relationship between gene trees and species trees. These models
account for gene duplication and loss, transfer or incomplete lineage sorting.
Some of them consider several types of events together, but none exists
currently that considers the full repertoire of processes that generate gene
trees along the species tree. Simulations as well as empirical studies on
genomic data show that combining gene tree-species tree models with models of
sequence evolution improves gene tree reconstruction. In turn, these better
gene trees provide a better basis for studying genome evolution or
reconstructing ancestral chromosomes and ancestral gene sequences. We predict
that gene tree-species tree methods that can deal with genomic data sets will
be instrumental to advancing our understanding of genomic evolution.Comment: Review article in relation to the "Mathematical and Computational
Evolutionary Biology" conference, Montpellier, 201
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