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Altman N.,Pennsylvania State University | Krzywinski M.,Canadas Michael Smith Genome science Center
Nature Methods | Year: 2015

The statistician knows...that in nature there never was a normal distribution, there never was a straight line, yet with normal and linear assumptions, known to be false, he can often derive results which match, to a useful approximation, those found in the real world. © 2015 Nature America, Inc.

Chikhi R.,Pennsylvania State University | Limasset A.,Ecole Normale Superieure de Cachan | Jackman S.,Canadas Michael Smith Genome science Center | Simpson J.T.,Ontario Cancer Institute | Medvedev P.,Pennsylvania State University
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2014

The de Bruijn graph plays an important role in bioinformatics, especially in the context of de novo assembly. However, the representation of the de Bruijn graph in memory is a computational bottleneck for many assemblers. Recent papers proposed a navigational data structure approach in order to improve memory usage. We prove several theoretical space lower bounds to show the limitations of these types of approaches. We further design and implement a general data structure (dbgfm) and demonstrate its use on a human whole-genome dataset, achieving space usage of 1.5 GB and a 46% improvement over previous approaches. As part of dbgfm, we develop the notion of frequency-based minimizers and show how it can be used to enumerate all maximal simple paths of the de Bruijn graph using only 43 MB of memory. Finally, we demonstrate that our approach can be integrated into an existing assembler by modifying the ABySS software to use dbgfm. © 2014 Springer International Publishing Switzerland.

Mandakova T.,Masaryk University | Joly S.,University of Quebec at Montreal | Krzywinski M.,Canadas Michael Smith Genome science Center | Mummenhoff K.,University of Osnabruck | Lysaka M.A.,Masaryk University
Plant Cell | Year: 2010

Mesopolyploid whole-genome duplication (WGD) was revealed in the ancestry of Australian Brassicaceae species with diploid-like chromosome numbers (n = 4 to 6). Multicolor comparative chromosome painting was used to reconstruct complete cytogenetic maps of the cryptic ancient polyploids. Cytogenetic analysis showed that the karyotype of the Australian Camelineae species descended from the eight ancestral chromosomes (n = 8) through allopolyploid WGD followed by the extensive reduction of chromosome number. Nuclear and maternal gene phylogenies corroborated the hybrid origin of the mesotetraploid ancestor and suggest that the hybridization event occurred ̃ 6 to 9 million years ago. The four, five, and six fusion chromosome pairs of the analyzed close relatives of Arabidopsis thaliana represent complex mosaics of duplicated ancestral genomic blocks reshuffled by numerous chromosome rearrangements. Unequal reciprocal translocations with or without preceeding pericentric inversions and purported end-to-end chromosome fusions accompanied by inactivation and/or loss of centromeres are hypothesized to be the main pathways for the observed chromosome number reduction. Our results underline the significance of multiple rounds of WGD in the angiosperm genome evolution and demonstrate that chromosome number per se is not a reliable indicator of ploidy level. © American Society of Plant Biologists.

Hasan M.R.,Texas College | Hasan M.R.,Canadas Michael Smith Genome science Center | Rahman M.,Texas College | Rahman M.,University of British Columbia | And 3 more authors.
Journal of Biological Chemistry | Year: 2010

Glucose 6-phosphate (G6P) is a metabolic intermediate with many possible cellular fates. In mycobacteria, G6P is a substrate for an enzyme, F 420-dependent glucose-6-phosphate dehydrogenase (Fgd), found in few bacterial genera. Intracellular G6P levels in six Mycobacterium sp. were remarkably higher (∼17-130-fold) than Escherichia coli and Bacillus megaterium. The high G6P level in Mycobacterium smegmatis may result from 10-25-fold higher activity of the gluconeogenic enzyme fructose-1,6- bisphosphatase when grown on glucose, glycerol, or acetate compared with B. megaterium and E. coli. In M. smegmatis this coincided with up-regulation of the first gluconeogenic enzyme, phosphoenolpyruvate carboxykinase, when acetate was the carbon source, suggesting a cellular program for maintaining high G6P levels. G6P was depleted in cells under oxidative stress induced by redox cycling agents plumbagin and menadione, whereas an fgd mutant of M. smegmatis used G6P less well under such conditions. The fgd mutant was more sensitive to these agents and, in contrast to wild type, was defective in its ability to reduce extracellular plumbagin and menadione. These data suggest that intracellular G6P in mycobacteria serves as a source of reducing power and, with the mycobacteria-specific Fgd-F420 system, plays a protective role against oxidative stress. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Krzywinski M.,Canadas Michael Smith Genome science Center
Molecular Cell | Year: 2016

Rapid and inexpensive single-cell sequencing is driving new visualizations of cancer instability and evolution. Krzywinski discusses how to present clone evolution plots in order to visualize temporal, phylogenetic, and spatial aspects of a tumor in a single static image. © 2016 Elsevier Inc.

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