Unraveling lipid metabolism in maize with time-resolved multi-omics data.

Maize is the cereal crop with the highest production worldwide, and its oil is a key energy resource. Improving the quantity and quality of maize oil requires a better understanding of lipid metabolism. To predict the function of maize genes involved in lipid biosynthesis, we assembled transcriptomic and lipidomic data sets from leaves of B73 and the high-oil line By804 in two distinct time-series experiments. The integrative analysis based on high-dimensional regularized regression yielded lipid-transcript associations indirectly validated by Gene Ontology and promoter motif enrichment analyses. The co-localization of lipid-transcript associations using the genetic mapping of lipid traits in leaves and seedlings of a B73 × By804 recombinant inbred line population uncovered 323 genes involved in the metabolism of phospholipids, galactolipids, sulfolipids and glycerolipids. The resulting association network further supported the involvement of 50 gene candidates in modulating levels of representatives from multiple acyl-lipid classes. Therefore, the proposed approach provides high-confidence candidates for experimental testing in maize and model plant species.

An integrated multi-layered analysis of the metabolic networks of different tissues uncovers key genetic components of primary metabolism in maize.

Primary metabolism plays a pivotal role in normal plant growth, development and reproduction. As maize is a major crop worldwide, the primary metabolites produced by maize plants are of immense importance from both calorific and nutritional perspectives. Here a genome-wide association study (GWAS) of 61 primary metabolites using a maize association panel containing 513 inbred lines identified 153 significant loci associated with the level of these metabolites in four independent tissues. The genome-wide expression level of 760 genes was also linked with metabolite levels within the same tissue. On average, the genetic variants at each locus or transcriptional variance of each gene identified here were estimated to have a minor effect (4.4-7.8%) on primary metabolic variation. Thirty-six loci or genes were prioritized as being worthy of future investigation, either with regard to functional characterization or for their utility for genetic improvement. This target list includes the well-known opaque 2 (O2) and lkr/sdh genes as well as many less well-characterized genes. During our investigation of these 36 loci, we analyzed the genetic components and variations underlying the trehalose, aspartate and aromatic amino acid pathways, thereby functionally characterizing four genes involved in primary metabolism in maize.

Metabolic robustness in young roots underpins a predictive model of maize hybrid performance in the field.

Heterosis has been extensively exploited for yield gain in maize (Zea mays L.). Here we conducted a comparative metabolomics-based analysis of young roots from in vitro germinating seedlings and from leaves of field-grown plants in a panel of inbred lines from the Dent and Flint heterotic patterns as well as selected F1 hybrids. We found that metabolite levels in hybrids were more robust than in inbred lines. Using state-of-the-art modeling techniques, the most robust metabolites from roots and leaves explained up to 37 and 44% of the variance in the biomass from plants grown in two distinct field trials. In addition, a correlation-based analysis highlighted the trade-off between defense-related metabolites and hybrid performance. Therefore, our findings demonstrated the potential of metabolic profiles from young maize roots grown under tightly controlled conditions to predict hybrid performance in multiple field trials, thus bridging the greenhouse-field gap.

Inheritance patterns in metabolism and growth in diallel crosses of Arabidopsis thaliana from a single growth habitat.

Metabolism is a key determinant of plant growth and modulates plant adaptive responses. Increased metabolic variation due to heterozygosity may be beneficial for highly homozygous plants if their progeny is to respond to sudden changes in the habitat. Here, we investigate the extent to which heterozygosity contributes to the variation in metabolism and size of hybrids of Arabidopsis thaliana whose parents are from a single growth habitat. We created full diallel crosses among seven parents, originating from Southern Germany, and analysed the inheritance patterns in primary and secondary metabolism as well as in rosette size in situ. In comparison to primary metabolites, compounds from secondary metabolism were more variable and showed more pronounced non-additive inheritance patterns which could be attributed to epistasis. In addition, we showed that glucosinolates, among other secondary metabolites, were positively correlated with a proxy for plant size. Therefore, our study demonstrates that heterozygosity in local A. thaliana population generates metabolic variation and may impact several tasks directly linked to metabolism.

Application of text mining to develop AOP-based mucus hypersecretion genesets and confirmation with in vitro and clinical samples.

Mucus hypersecretion contributes to lung function impairment observed in COPD (chronic obstructive pulmonary disease), a tobacco smoking-related disease. A detailed mucus hypersecretion adverse outcome pathway (AOP) has been constructed from literature reviews, experimental and clinical data, mapping key events (KEs) across biological organisational hierarchy leading to an adverse outcome. AOPs can guide the development of biomarkers that are potentially predictive of diseases and support the assessment frameworks of nicotine products including electronic cigarettes. Here, we describe a method employing manual literature curation supported by a focused automated text mining approach to identify genes involved in 5 KEs contributing to decreased lung function observed in tobacco-related COPD. KE genesets were subsequently confirmed by unsupervised clustering against 3 different transcriptomic datasets including (1) in vitro acute cigarette smoke and e-cigarette aerosol exposure, (2) in vitro repeated incubation with IL-13, and (3) lung biopsies from COPD and healthy patients. The 5 KE genesets were demonstrated to be predictive of cigarette smoke exposure and mucus hypersecretion in vitro, and less conclusively predict the COPD status of lung biopsies. In conclusion, using a focused automated text mining and curation approach with experimental and clinical data supports the development of risk assessment strategies utilising AOPs.

Metabolic reconfiguration of strawberry physiology in response to postharvest practices.

The strawberry fruit is perishable due to its high water content and soft texture, yet exhibits pleasant organoleptic and nutritional profile. Here we conducted a metabolomics-driven analysis followed by linear modelling to dissect the molecular processes in strawberry postharvest. Fruits from five cultivars were harvested and refrigerated during a ten-day period under three different atmospheres: ambient, CO2-enriched and O3-enriched. These analyses revealed that metabolites involved in, (i) organoleptic and nutritional properties; (ii) stress tolerance displayed duration and postharvest treatment-dependent levels. Ozone-enriched atmosphere appears to counteract postharvest negative effects, with fruits exhibiting lower levels of fermentative metabolites when compared to fruits kept in an ambient atmosphere. Furthermore, metabolic reconfiguration towards the synthesis of protective metabolites of those fruits can possibly confer enhanced tolerance to postharvest abiotic stresses. Finally, results from the linear modelling identified metabolites which could be used as biomarkers to assess strawberry quality during its postharvest shelf life.

Regression-Based Modeling of Complex Plant Traits Based on Metabolomics Data.

Bridging metabolomics with plant phenotypic responses is challenging. Multivariate analyses account for the existing dependencies among metabolites, and regression models in particular capture such dependencies in search for association with a given trait. However, special care should be undertaken with metabolomics data. Here we propose a modeling workflow that considers all caveats imposed by such large data sets.

Classification-driven framework to predict maize hybrid field performance from metabolic profiles of young parental roots.

Maize (Zea mays L.) is a staple food whose production relies on seed stocks that largely comprise hybrid varieties. Therefore, knowledge about the molecular determinants of hybrid performance (HP) in the field can be used to devise better performing hybrids to address the demands for sustainable increase in yield. Here, we propose and test a classification-driven framework that uses metabolic profiles from in vitro grown young roots of parental lines from the Dent × Flint maize heterotic pattern to predict field HP. We identify parental analytes that best predict the metabolic inheritance patterns in 328 hybrids. We then demonstrate that these analytes are also predictive of field HP (0.64 ≥ r ≥ 0.79) and discriminate hybrids of good performance (accuracy of 87.50%). Therefore, our approach provides a cost-effective solution for hybrid selection programs.

Genetic diversity of strawberry germplasm using metabolomic biomarkers.

High-throughput metabolomics technologies can provide the quantification of metabolites levels across various biological processes in different tissues, organs and species, allowing the identification of genes underpinning these complex traits. Information about changes of metabolites during strawberry development and ripening processes is key to aiding the development of new approaches to improve fruit attributes. We used network-based methods and multivariate statistical approaches to characterize and investigate variation in the primary and secondary metabolism of seven domesticated and seven wild strawberry fruit accessions at three different fruit development and ripening stages. Our results demonstrated that Fragaria sub-species can be identified solely based on the gathered metabolic profiles. We also showed that domesticated accessions displayed highly similar metabolic changes due to shared domestication history. Differences between domesticated and wild accessions were detected at the level of metabolite associations which served to rank metabolites whose regulation was mostly altered in the process of domestication. The discovery of comprehensive metabolic variation among strawberry accessions offers opportunities to probe into the genetic basis of variation, providing insights into the pathways to relate metabolic variation with important traits.

Genomics-based strategies for the use of natural variation in the improvement of crop metabolism.

Next-generation genomics holds great potential in the study of plant phenotypic variation. With several crop reference genomes now available, the affordable costs of de novo genome assembly or target resequencing offer the opportunity to mine the enormous amount of genetic diversity hidden in crop wild relatives. Wide introgressions from these wild ancestors species or land races represent a possible strategy to improve cultivated varieties. In this review, we discuss the mechanisms underlying metabolic diversity within plant species and the possible strategies (and barriers) to introgress novel metabolic traits into cultivated varieties. We show how deep genomic surveys uncover various types of structural variants from extended gene pools of major crops and highlight how this variation may be used for the improvement of crop metabolism.