ORCID Profile
0000-0002-9689-5915
Current Organisations
Commonwealth Scientific and Industrial Research Organisation
,
Children's Medical Research Institute
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Publisher: Cold Spring Harbor Laboratory
Date: 29-11-2018
DOI: 10.1101/481101
Publisher: Springer Science and Business Media LLC
Date: 30-07-2020
DOI: 10.1038/S41467-020-17641-3
Abstract: Reproducible research is the bedrock of experimental science. To enable the deployment of large-scale proteomics, we assess the reproducibility of mass spectrometry (MS) over time and across instruments and develop computational methods for improving quantitative accuracy. We perform 1560 data independent acquisition (DIA)-MS runs of eight s les containing known proportions of ovarian and prostate cancer tissue and yeast, or control HEK293T cells. Replicates are run on six mass spectrometers operating continuously with varying maintenance schedules over four months, interspersed with ~5000 other runs. We utilise negative controls and replicates to remove unwanted variation and enhance biological signal, outperforming existing methods. We also design a method for reducing missing values. Integrating these computational modules into a pipeline (ProNorM), we mitigate variation among instruments over time and accurately predict tissue proportions. We demonstrate how to improve the quantitative analysis of large-scale DIA-MS data, providing a pathway toward clinical proteomics.
Publisher: Institute of Mathematical Statistics
Date: 2010
DOI: 10.1214/10-EJS581
Publisher: Springer Science and Business Media LLC
Date: 27-09-2014
DOI: 10.1007/S00122-014-2401-0
Abstract: We present a novel estimator for map construction in the presence of segregation distortion which is highly computationally efficient. For multi-parental designs this estimator outperforms methods that do not account for segregation distortion, at no extra computational cost. Inclusion of genetic markers exhibiting segregation distortion in a linkage map can result in biased estimates of genetic distance and distortion of map positions. Removal of distorted markers is hence a typical filtering criterion however, this may result in exclusion of biologically interesting regions of the genome such as introgressions and translocations. Estimation of additional parameters characterizing the distortion is computationally slow, as it relies on estimation via the Expectation Maximization algorithm or a higher dimensional numerical optimisation. We propose a robust M-estimator (RM) capable of handling tens of thousands of distorted markers from a single linkage group. We show via simulation that for multi-parental designs the RM estimator can perform much better than uncorrected estimation, at no extra computational cost. We then apply the RM estimator to chromosome 2B in wheat in a multi-parent population segregating for the Sr36 introgression, a known transmission distorter. The resulting map contains over 700 markers, and is consistent with maps constructed from crosses which do not exhibit segregation distortion.
Publisher: Springer Science and Business Media LLC
Date: 19-05-2018
Publisher: Cold Spring Harbor Laboratory
Date: 31-03-2019
DOI: 10.1101/594317
Abstract: Identifying the genetic architecture of complex traits requires access to populations with sufficient genetic ersity and recombination. Multi-parent Advanced Generation InterCross (MAGIC) populations are a powerful resource due to their balanced population structure, allelic ersity and enhanced recombination. However, implementing a MAGIC population in complex polyploids such as wheat is not trivial, as wheat harbours many introgressions, inversions and other genetic factors that interfere with linkage mapping. By utilising a comprehensive crossing strategy, additional rounds of mixing and novel genotype calling approaches, we developed a bread wheat eight parent MAGIC population made up of more than 3000 fully genotyped recombinant inbred lines derived from 2151 distinct crosses, and achieved a dense genetic map covering the complete genome. Further rounds of inter-crossing led to increased recombination in inbred lines, as expected. The comprehensive and novel approaches taken in the development and analysis of this population provide a platform for genetic discovery in bread wheat. We identify previously unreported structural variation highlighted by segregation distortion, along with the identification of epistatic allelic interactions between specific founders. We demonstrate the ability to conduct high resolution QTL mapping using the number of recombination events as a trait, and identify several significant QTLs explaining greater than 50% of the variance. We report on a novel and effective resource for genomic and trait exploration in hexaploid wheat, that can be used to detect small genetic effects and epistatic interactions due to the high level of recombination and large number of lines. The interactions and genetic effects identified provide a basis for ongoing research to understand the basis of allelic frequencies across the genome, particularly where economically important loci are involved.
Publisher: Oxford University Press (OUP)
Date: 06-05-2020
DOI: 10.1093/BIOINFORMATICS/BTAA295
Abstract: Genetic map construction is a foundational step in the analysis of structured experimental populations. For markers that hybridize to several genetically similar locations, or where several alleles are present (such as in multiparental populations), current methods often discard the marker or incorrectly call the genotypes. These errors result in information loss, or incorrect genotypes that can corrupt map construction. We present a new approach for simultaneously performing genetic map construction and marker calling. Our new approach allows the calling of a larger number of markers, a larger number of unique alleles per marker and the correct use of markers which hybridize to multiple genetically similar locations. We demonstrate our new approach using simulations, a biparental wheat population and an eight-parent population of spring bread wheat. Applying our method to the eight-parent population increased the number of mapped markers by 71%. We show that the new genetic map allows the investigation of synteny in ways that were not previously possible in that dataset. The method described in this article has been incorporated into R package mpMap2. It is available from CRAN and also from ohan-shah/mpMap2. Supplementary data are available at Bioinformatics online.
Location: Australia
Location: No location found
No related grants have been discovered for Rohan Shah.