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831.
Phillip Andrew Richmond Alice Mary Kaye Godfrain Jacques Kounkou Tamar Vered Av-Shalom Wyeth W. Wasserman 《PLoS computational biology》2021,17(3)
Across the life sciences, processing next generation sequencing data commonly relies upon a computationally expensive process where reads are mapped onto a reference sequence. Prior to such processing, however, there is a vast amount of information that can be ascertained from the reads, potentially obviating the need for processing, or allowing optimized mapping approaches to be deployed. Here, we present a method termed FlexTyper which facilitates a “reverse mapping” approach in which high throughput sequence queries, in the form of k-mer searches, are run against indexed short-read datasets in order to extract useful information. This reverse mapping approach enables the rapid counting of target sequences of interest. We demonstrate FlexTyper’s utility for recovering depth of coverage, and accurate genotyping of SNP sites across the human genome. We show that genotyping unmapped reads can correctly inform a sample’s population, sex, and relatedness in a family setting. Detection of pathogen sequences within RNA-seq data was sensitive and accurate, performing comparably to existing methods, but with increased flexibility. We present two examples of ways in which this flexibility allows the analysis of genome features not well-represented in a linear reference. First, we analyze contigs from African genome sequencing studies, showing how they distribute across families from three distinct populations. Second, we show how gene-marking k-mers for the killer immune receptor locus allow allele detection in a region that is challenging for standard read mapping pipelines. The future adoption of the reverse mapping approach represented by FlexTyper will be enabled by more efficient methods for FM-index generation and biology-informed collections of reference queries. In the long-term, selection of population-specific references or weighting of edges in pan-population reference genome graphs will be possible using the FlexTyper approach. FlexTyper is available at https://github.com/wassermanlab/OpenFlexTyper. 相似文献
832.
Rivka Beitner Shoshana Haberman Jardena Nordenberg Tamar Jehuda Cohen 《Biochimica et Biophysica Acta (BBA)/General Subjects》1978,542(3):537-541
A striking reduction in the levels of glucose 1,6-diphosphate and an increase in cyclic GMP were found in muscle from dystrophic mice. Concomitant to these changes, the allosteric activity of phosphofructokinase was found to be markedly reduced. These findings could offer an explanation for the observed reduction in glycolysis in the dystrophic muscle. 相似文献
833.
834.
Tamar Farfel-Becker Einat B. Vitner Anthony H. Futerman 《Disease models & mechanisms》2011,4(6):746-752
Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD. 相似文献
835.
836.
The parasitic larva of Telenomus remus is surrounded by giant cells throughout its first instar. These cells arise in the embryonic serosa of the parasite and grow in size, starting with a radius of 5nm and ending with 27nm. Young cells are round and mononuclear, whereas older ones are often polynuclear and have varied, irregular contours. Most cells are profusely vacuolated, the vacuoles being especially large in some of the older cells. Only a few of the giant cells are devoured by the first instar parasite larva, but all disappear at the end of this stage. No giant cells seem to be produced by supernumerary larvae. Once the parasite egg hatches, the host tissue disintegrates almost instantaneously. 相似文献