Lindner, Martin Michael Serenus
[VerfasserIn]
;
PD Bernhard Renard
[MitwirkendeR];
Jun.- Tobias Marschall
[MitwirkendeR]
Computational methods for the identification and quantification of microbial organisms in metagenomes ; Computergestützte Methoden zur Bestimmung und Quantifizierung von Mikroorganismen in Metagenomen
Titel:
Computational methods for the identification and quantification of microbial organisms in metagenomes ; Computergestützte Methoden zur Bestimmung und Quantifizierung von Mikroorganismen in Metagenomen
Beteiligte:
Lindner, Martin Michael Serenus
[VerfasserIn]
Erschienen:
Freie Universität Berlin: Refubium (FU Berlin), 2015
Anmerkungen:
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Beschreibung:
Metagenomics allows analyzing genomic material taken directly from the environment. In contrast to classical genomics, no purification of single organisms is performed and therefore the extracted genomic material reflects the composition of the original microbial community. The possible applications of metagenomics are manifold and the field has become increasingly popular due to the recent improvements in sequencing technologies. One of the most fundamental challenges in metagenomics is the identification and quantification of organisms in a sample, called taxonomic profiling. In this work, we present approaches to the following current problems in taxonomic profiling: First, differentiation between closely related organisms in metagenomic samples is still challenging. Second, the identification of novel organisms in metagenomic samples poses problems to current taxonomic profiling methods, especially when there is no suitable reference genome available. The contribution of this thesis comprises three major projects. First, we introduce the Genome Abundance Similarity Correction (GASiC) algorithm, a method that allows differentiating between and quantifying highly similar microbial organisms in a metagenomic sample. The method first estimates the similarities between the available reference genomes with a simulation approach. Based on the similarities, GASiC corrects the observed abundances of each reference genome using a non-negative lasso approach. In several experiments we showed that the abundance estimates are highly accurate and reduce the error compared to current approaches by 5% to 60%. The approach was also successfully applied to metaproteomics. In the second project, we developed a statistical framework to fit mixtures of discrete distribution functions to the histograms of sequencing coverage depth after mapping metagenomic reads to reference genomes. We tailored a family of distributions for this particular application and modified the expectation-maximization algorithm to also fit discrete ...