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Integrated analysis of transcript, protein and metabolite data to study lignin biosynthesis in hybrid aspen
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Medicine, Umeå Life Science Centre (ULSC).
Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).ORCID iD: 0000-0002-1543-7358
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2009 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 8, no 1, 199-210 p.Article in journal (Refereed) Published
Abstract [en]

Tree biotechnology will soon reach a mature state where it will influence the overall supply of fiber, energy and wood products. We are now ready to make the transition from identifying candidate genes, controlling important biological processes, to discovering the detailed molecular function of these genes on a broader, more holistic, systems biology level. In this paper, a strategy is outlined for informative data generation and integrated modeling of systematic changes in transcript, protein and metabolite profiles measured from hybrid aspen samples. The aim is to study characteristics of common changes in relation to genotype-specific perturbations affecting the lignin biosynthesis and growth. We show that a considerable part of the systematic effects in the system can be tracked across all platforms and that the approach has a high potential value in functional characterization of candidate genes.

Place, publisher, year, edition, pages
2009. Vol. 8, no 1, 199-210 p.
Keyword [en]
Combined profiling, O2PLS, Chemometrics, Populus, Lignin biosynthesis
National Category
Bioinformatics and Systems Biology
URN: urn:nbn:se:umu:diva-11303DOI: 10.1021/pr800298sOAI: diva2:150974
Available from: 2009-01-13 Created: 2009-01-13 Last updated: 2015-05-06
In thesis
1. Latent variable based computational methods for applications in life sciences: Analysis and integration of omics data sets
Open this publication in new window or tab >>Latent variable based computational methods for applications in life sciences: Analysis and integration of omics data sets
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

With the increasing availability of high-throughput systems for parallel monitoring of multiple variables, e.g. levels of large numbers of transcripts in functional genomics experiments, massive amounts of data are being collected even from single experiments. Extracting useful information from such systems is a non-trivial task that requires powerful computational methods to identify common trends and to help detect the underlying biological patterns. This thesis deals with the general computational problems of classifying and integrating high-dimensional empirical data using a latent variable based modeling approach. The underlying principle of this approach is that a complex system can be characterized by a few independent components that characterize the systematic properties of the system. Such a strategy is well suited for handling noisy, multivariate data sets with strong multicollinearity structures, such as those typically encountered in many biological and chemical applications.

The main foci of the studies this thesis is based upon are applications and extensions of the orthogonal projections to latent structures (OPLS) method in life science contexts. OPLS is a latent variable based regression method that separately describes systematic sources of variation that are related and unrelated to the modeling aim (for instance, classifying two different categories of samples). This separation of sources of variation can be used to pre-process data, but also has distinct advantages for model interpretation, as exemplified throughout the work. For classification cases, a probabilistic framework for OPLS has been developed that allows the incorporation of both variance and covariance into classification decisions. This can be seen as a unification of two historical classification paradigms based on either variance or covariance. In addition, a non-linear reformulation of the OPLS algorithm is outlined, which is useful for particularly complex regression or classification tasks.

The general trend in functional genomics studies in the post-genomics era is to perform increasingly comprehensive characterizations of organisms in order to study the associations between their molecular and cellular components in greater detail. Frequently, abundances of all transcripts, proteins and metabolites are measured simultaneously in an organism at a current state or over time. In this work, a generalization of OPLS is described for the analysis of multiple data sets. It is shown that this method can be used to integrate data in functional genomics experiments by separating the systematic variation that is common to all data sets considered from sources of variation that are specific to each data set.

Abstract [sv]

Funktionsgenomik är ett forskningsområde med det slutgiltiga målet att karakterisera alla gener i ett genom hos en organism. Detta inkluderar studier av hur DNA transkriberas till mRNA, hur det sedan translateras till proteiner och hur dessa proteiner interagerar och påverkar organismens biokemiska processer. Den traditionella ansatsen har varit att studera funktionen, regleringen och translateringen av en gen i taget. Ny teknik inom fältet har dock möjliggjort studier av hur tusentals transkript, proteiner och små molekyler uppträder gemensamt i en organism vid ett givet tillfälle eller över tid. Konkret innebär detta även att stora mängder data genereras även från små, isolerade experiment. Att hitta globala trender och att utvinna användbar information från liknande data-mängder är ett icke-trivialt beräkningsmässigt problem som kräver avancerade och tolkningsbara matematiska modeller.

Denna avhandling beskriver utvecklingen och tillämpningen av olika beräkningsmässiga metoder för att klassificera och integrera stora mängder empiriskt (uppmätt) data. Gemensamt för alla metoder är att de baseras på latenta variabler: variabler som inte uppmätts direkt utan som beräknats från andra, observerade variabler. Detta koncept är väl anpassat till studier av komplexa system som kan beskrivas av ett fåtal, oberoende faktorer som karakteriserar de huvudsakliga egenskaperna hos systemet, vilket är kännetecknande för många kemiska och biologiska system. Metoderna som beskrivs i avhandlingen är generella men i huvudsak utvecklade för och tillämpade på data från biologiska experiment.

I avhandlingen demonstreras hur dessa metoder kan användas för att hitta komplexa samband mellan uppmätt data och andra faktorer av intresse, utan att förlora de egenskaper hos metoden som är kritiska för att tolka resultaten. Metoderna tillämpas för att hitta gemensamma och unika egenskaper hos regleringen av transkript och hur dessa påverkas av och påverkar små molekyler i trädet poppel. Utöver detta beskrivs ett större experiment i poppel där relationen mellan nivåer av transkript, proteiner och små molekyler undersöks med de utvecklade metoderna.

Place, publisher, year, edition, pages
Umeå: Kemi, 2008. 50 p.
Chemometrics, orthogonal projections to latent structures, OPLS, O2PLS, K-OPLS, kernel-based, non-linear, regression, classification, Populus
National Category
Chemical Sciences
urn:nbn:se:umu:diva-1616 (URN)978-91-7264-541-7 (ISBN)
Public defence
2008-05-09, KB3A9, KBC-huset, Umeå Universitet, Umeå, 10:00 (English)
Available from: 2008-04-17 Created: 2008-04-17 Last updated: 2009-06-18Bibliographically approved

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Bylesjö, MaxNilsson, RobertGrönlund, AndreasJansson, StefanKarlsson, JanMoritz, ThomasWingsle, GunnarTrygg, Johan
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Department of ChemistryUmeå Life Science Centre (ULSC)Department of Plant PhysiologyUmeå Plant Science Centre (UPSC)
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