Laura‐Jayne Gardiner

Sci-Tech Daresbury

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Anthony Hall

Earlham Institute

Ritesh Krishna

Sci-Tech Daresbury

Neil Hall

University of East Anglia

Ryan Joynson

Norwich Research Park

Niina Haiminen

IBM (United States)

Laxmi Parida

IBM Research - Thomas J. Watson Research Center

Anna Paola Carrieri

Sci-Tech Daresbury

Michael W. Bevan

John Innes Centre

Lisa Olohan

University of Liverpool

Edward O. Pyzer‐Knapp

Sci-Tech Daresbury

Cooperative Institutions

University of Liverpool

Norwich Research Park

University of Nottingham

Sci-Tech Daresbury

John Innes Centre

Earlham Institute

Leibniz Institute of Plant Genetics and Crop Plant Research

Rothamsted Research

United States Department of Agriculture

Centro Internacional de Mejoramiento de Maíz Y Trigo

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Elsevier eBooks (2019)

Eva Bauer Alison R. Bentley Hans‐Joachim Braun Susanne Dreisigacker Tzion Fahima

10.1016/b978-0-08-102163-7.09990-7

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Analysis of the recombination landscape of hexaploid bread wheat reveals genes controlling recombination and gene conversion frequency

bioRxiv (Cold Spring Harbor Laboratory) (2019)

Laura‐Jayne Gardiner Luzie U. Wingen Paul Bailey Ryan Joynson Thomas Brabbs

Abstract Sequence exchange between homologous chromosomes through crossing over and gene conversion is highly conserved among eukaryotes, contributing to genome stability and genetic diversity. Lack of recombination limits breeding efforts in crops, therefore increasing recombination rates can reduce linkage-drag and generate new genetic combinations. We use computational analysis of 13 recombinant inbred mapping populations to assess crossover and gene conversion frequency in the hexaploid genome of wheat ( Triticum aestivum ). We observe that high frequency crossover sites are shared between populations and that closely related parental founders lead to populations with more similar crossover patterns. We demonstrate that gene conversion is more prevalent and covers more of the genome in wheat than in other plants, making it a critical process in the generation of new haplotypes, particularly in centromeric regions where crossovers are rare. We have identified QTL for altered gene conversion and crossover frequency and confirm functionality for a novel RecQ helicase gene that belongs to an ancient clade that is missing in some plant lineages including Arabidopsis . This is the first gene to be demonstrated to be involved in gene conversion in wheat. Harnessing the RecQ helicase has the potential to break linkage-drag utilizing widespread gene conversions.

RecQ helicase

Gene conversion

Chromosomal crossover

Common wheat

10.1101/539684

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Scalable in-memory processing of omics workflows

Computational and Structural Biotechnology Journal (2022)

Vadim Elisseev Laura‐Jayne Gardiner Ritesh Krishna

We present a proof of concept implementation of the in-memory computing paradigm that we use to facilitate the analysis of metagenomic sequencing reads. In doing so we compare the performance of POSIX™file systems and key-value storage for omics data, and we show the potential for integrating high-performance computing (HPC) and cloud native technologies. We show that in-memory key-value storage offers possibilities for improved handling of omics data through more flexible and faster data processing. We envision fully containerized workflows and their deployment in portable micro-pipelines with multiple instances working concurrently with the same distributed in-memory storage. To highlight the potential usage of this technology for event driven and real-time data processing, we use a biological case study focused on the growing threat of antimicrobial resistance (AMR). We develop a workflow encompassing bioinformatics and explainable machine learning (ML) to predict life expectancy of a population based on the microbiome of its sewage while providing a description of AMR contribution to the prediction. We propose that in future, performing such analyses in 'real-time' would allow us to assess the potential risk to the population based on changes in the AMR profile of the community.

10.1016/j.csbj.2022.04.014

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Bisulphite Sequencing v1

Fu-Hao Lu N. J. McKenzie Laura‐Jayne Gardiner Ming‐Cheng Luo Anthony Hall

This protocol describes how we generated and processed the bisulphite sequencing data

10.17504/protocols.io.75vhq66

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Chromosome 3DL Arm Assembly and Annotation v1

Fu-Hao Lu N. J. McKenzie Laura‐Jayne Gardiner Ming‐Cheng Luo Anthony Hall

This protocol descriobed the detailed procedures how we made the chromosome 3D long arm pseudomolecule in hexaploid wheat (Triticum aestivum, AABBDD).

Long arm

10.17504/protocols.io.75shq6e

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Assay for Transposase-Accessible Chromatin (ATAC) Sequencing v1

Fu-Hao Lu Neil McKenzie Laura‐Jayne Gardiner Ming‐Cheng Luo Anthony Hall

This protocol describes how we generated and processed ATAC-seq data

Transposase

10.17504/protocols.io.75whq7e

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A framework for gene mapping in wheat demonstrated using the Yr7 yellow rust resistance gene

PLoS ONE (2020)

Laura‐Jayne Gardiner Pauline Bansept‐Basler Mohamed El‐Soda Anthony Hall Donal M. O’Sullivan

We used three approaches to map the yellow rust resistance gene Yr7 and identify associated SNPs in wheat. First, we used a traditional QTL mapping approach using a double haploid (DH) population and mapped Yr7 to a low-recombination region of chromosome 2B. To fine map the QTL, we then used an association mapping panel. Both populations were SNP array genotyped allowing alignment of QTL and genome-wide association scans based on common segregating SNPs. Analysis of the association panel spanning the QTL interval, narrowed the interval down to a single haplotype block. Finally, we used mapping-by-sequencing of resistant and susceptible DH bulks to identify a candidate gene in the interval showing high homology to a previously suggested Yr7 candidate and to populate the Yr7 interval with a higher density of polymorphisms. We highlight the power of combining mapping-by-sequencing, delivering a complete list of gene-based segregating polymorphisms in the interval with the high recombination, low LD precision of the association mapping panel. Our mapping-by-sequencing methodology is applicable to any trait and our results validate the approach in wheat, where with a near complete reference genome sequence, we are able to define a small interval containing the causative gene.

Candidate gene

Family-based QTL mapping

Association mapping

Genetic Association

10.1371/journal.pone.0231157

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Combining explainable machine learning, demographic and multi-omic data to inform precision medicine strategies for inflammatory bowel disease

PLoS ONE (2022)

Laura‐Jayne Gardiner Anna Paola Carrieri Karen Bingham Graeme Macluskie David Bunton

Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, affect several million individuals worldwide. These diseases are heterogeneous at the clinical, immunological and genetic levels and result from complex host and environmental interactions. Investigating drug efficacy for IBD can improve our understanding of why treatment response can vary between patients. We propose an explainable machine learning (ML) approach that combines bioinformatics and domain insight, to integrate multi-modal data and predict inter-patient variation in drug response. Using explanation of our models, we interpret the ML models' predictions to infer unique combinations of important features associated with pharmacological responses obtained during preclinical testing of drug candidates in ex vivo patient-derived fresh tissues. Our inferred multi-modal features that are predictive of drug efficacy include multi-omic data (genomic and transcriptomic), demographic, medicinal and pharmacological data. Our aim is to understand variation in patient responses before a drug candidate moves forward to clinical trials. As a pharmacological measure of drug efficacy, we measured the reduction in the release of the inflammatory cytokine TNFα from the fresh IBD tissues in the presence/absence of test drugs. We initially explored the effects of a mitogen-activated protein kinase (MAPK) inhibitor; however, we later showed our approach can be applied to other targets, test drugs or mechanisms of interest. Our best model predicted TNFα levels from demographic, medicinal and genomic features with an error of only 4.98% on unseen patients. We incorporated transcriptomic data to validate insights from genomic features. Our results showed variations in drug effectiveness (measured by ex vivo assays) between patients that differed in gender, age or condition and linked new genetic polymorphisms to patient response variation to the anti-inflammatory treatment BIRB796 (Doramapimod). Our approach models IBD drug response while also identifying its most predictive features as part of a transparent ML precision medicine strategy.

Efficacy

Personalized Medicine

Omics

Drug repositioning

10.1371/journal.pone.0263248

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A haplotype map of allohexaploid wheat reveals distinct patterns of selection on homoeologous genomes

Genome Biology (2015)

Katherine W. Jordan Shichen Wang Yanni Lun Laura‐Jayne Gardiner Ron MacLachlan

Bread wheat is an allopolyploid species with a large, highly repetitive genome. To investigate the impact of selection on variants distributed among homoeologous wheat genomes and to build a foundation for understanding genotype-phenotype relationships, we performed population-scale re-sequencing of a diverse panel of wheat lines.A sample of 62 diverse lines was re-sequenced using the whole exome capture and genotyping-by-sequencing approaches. We describe the allele frequency, functional significance, and chromosomal distribution of 1.57 million single nucleotide polymorphisms and 161,719 small indels. Our results suggest that duplicated homoeologous genes are under purifying selection. We find contrasting patterns of variation and inter-variant associations among wheat genomes; this, in addition to demographic factors, could be explained by differences in the effect of directional selection on duplicated homoeologs. Only a small fraction of the homoeologous regions harboring selected variants overlapped among the wheat genomes in any given wheat line. These selected regions are enriched for loci associated with agronomic traits detected in genome-wide association studies.Evidence suggests that directional selection in allopolyploids rarely acted on multiple parallel advantageous mutations across homoeologous regions, likely indicating that a fitness benefit could be obtained by a mutation at any one of the homoeologs. Additional advantageous variants in other homoelogs probably either contributed little benefit, or were unavailable in populations subjected to directional selection. We hypothesize that allopolyploidy may have increased the likelihood of beneficial allele recovery by broadening the set of possible selection targets.

Human genetics

10.1186/s13059-015-0606-4

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Citations (231)

Additional file 7 of Re-purposing software for functional characterization of the microbiome

Figshare (2021)

Laura‐Jayne Gardiner Niina Haiminen Filippo Utro Laxmi Parida Ed Seabolt

Additional file 6. Building a reference database using the GO taxonomy (Kaiju).

Characterization

10.6084/m9.figshare.13550949

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