Chapter 17 THE HUMAN METABOLOME

The human metabolome is best understood by analogy to the human genome, i.e. where the human genome is the set of all genes in a human, the human metabolome is the set of all metabolites in a human. Whereas the science of genomics is based upon a genome, the science of metabolomics is grounded in a metabolome. To continue the genome/metabolome analogy, it should be apparent that any published huma

www.niss.org A Tale of Two Matrix Factorizations

In statistical practice, rectangular tables of numeric data are commonplace, and are often analyzed using dimension reduction methods like the singular value decomposition (SVD) and its close cousin, principal component analysis (PCA). This analysis produces score and loading matrices representing the rows and the columns of the original table and these matrices may be used for both prediction purposes and to gain structural understanding of the data. In some tables, the data entries are necessarily non-negative (apart, perhaps, from some small random noise), and so the matrix factors meant to represent them should arguably also contain only non-negative elements. This thinking, and the desire for parsimony, underlies such techniques as rotating factors in a search for “simple structure. ” These attempts to transform score or loading matrices of mixed sign into nonnegative, parsimonious forms are however indirect and at best imperfect. The recent development of non-negative matrix factorization, or NMF, is an attractive alternative. Rather than attempt to transform a loading or score matrix of mixed signs into one with only non-negative elements, it directly seeks matrix factors containing only non-negative elements. The resulting factorization often leads to substantial improvements in interpretability of the factors. We illustrate this potentia

Comparative physiological and metabolomics analysis of wheat (Triticum aestivum L.) following post-anthesis heat stress.

Genetic improvement for stress tolerance requires a solid understanding of biochemical processes involved with different physiological mechanisms and their relationships with different traits. The objective of this study was to demonstrate genetic variability in altered metabolic levels in a panel of six wheat genotypes in contrasting temperature regimes, and to quantify the correlation between those metabolites with different traits. In a controlled environment experiment, heat stress (35:28 ± 0.08°C) was initiated 10 days after anthesis. Flag leaves were collected 10 days after heat treatment to employ an untargeted metabolomics profiling using LC-HRMS based technique called IROA. High temperature stress produced significant genetic variations for cell and thylakoid membrane damage, and yield related traits. 64 known metabolites accumulated 1.5 fold of higher or lower due to high temperature stress. In general, metabolites that increased the most under heat stress (L-tryptophan, pipecolate) showed negative correlation with different traits. Contrary, the metabolites that decreased the most under heat stress (drummondol, anthranilate) showed positive correlation with the traits. Aminoacyl-tRNA biosysnthesis and plant secondary metabolite biosynthesis pathways were most impacted by high temperature stress. The robustness of metabolic change and their relationship with phenotypes renders those metabolites as potential bio-markers for genetic improvement

Derivational Paradigm in Word Formation

The morphological paradigm as a theoretical construct has a central role in explaining inflectional word formation, particularly in Word & Paradigm approaches to morphology. In contrast, research into the role of paradigm in derivation has been programmatic as well as fragmentary. In this paper I investigate the extent to which patterns of relationships among derived words constitute a derivational paradigm. A more comprehensive and precise characterization of derivational paradigm is provided based on a unified treatment of inflection and derivation. Previous diachronic-oriented research (van Marle, 1984; Pounder, 2000) is complemented by a dynamic model I propose for representing the role of derivational paradigms in synchronic word-formation. The proposed model captures local vs. non-local derivational associations as identified via what I refer to as the Paradigmatic Derivate Generalization (PDG). Using the model and a generalized notion of paradigm derived from the rule-patterns of Bochner (1993), a variety of derivational processes in English, French, Tigre and Lithuanian are analyzed to identify the paradigmatic relationships upon which word formation in those languages is dependent. The suitability of the model for implementation using word-formation rules is also demonstrated through an analysis of a fragmen

Metabolomics and Natural-Products Strategies to Study Chemical Ecology in Nematodes

Synopsis This review provides an overview of two complementary approaches to identify biologically active compounds for studies in chemical ecology. The first is activity-guided fractionation and the second is metabolomics, particularly focusing on a new liquid chromatography-mass spectrometry-based method called isotopic ratio outlier analysis. To illustrate examples using these approaches, we review recent experiments using Caenorhabditis elegans and related freeliving nematodes

Quantitative Metabolomics Using Isotope Residue Outlier Analysis (IROA ® ) with Internal Standards

Various research strategies involving biomarker discovery and mechanistic studies in system biology depend on reproducible and reliable quantification of all metabolites from tissue(s) of interest. Contemporary analytical methods rely on mass spectrometry-based targeted and/or untargeted metabolomics platforms. The robustness of these analyses depends on the cleanliness of the samples, accuracy of the database, resolution of the instrument, and, the most variable of the list, the personal preferences of the researcher and the instrument operator. In this chapter, we introduce a simple method to prepare murine liver samples and carry it through the Isotope Ratio Outlier Analysis (IROA ) pipeline. This pipeline encompasses sample preparation, LC-MS-based peak acquisition, proprietary software-based library creation, normalization, and quantification of metabolites. IROA offers a unique platform to create and normalize a local library and account for run-to-run variability over years of acquisition using the internal standards (IROA -IS) and long-term reference standards (IROA -LTRS)

Fold change results for the top 12 metabolites showing the greatest increase or decrease in metabolite concentration in heat stressed plants compared to control plants.

<p>Fold change results for the top 12 metabolites showing the greatest increase or decrease in metabolite concentration in heat stressed plants compared to control plants.</p