TY - JOUR A1 - David, Laszlo A1 - Marashi, Sayed-Amir A1 - Larhlimi, Abdelhalim A1 - Mieth, Bettina A1 - Bockmayr, Alexander T1 - FFCA a feasibility-based method for flux coupling analysis of metabolic networks JF - BMC bioinformatics N2 - Background: Flux coupling analysis (FCA) is a useful method for finding dependencies between fluxes of a metabolic network at steady-state. FCA classifies reactions into subsets (called coupled reaction sets) in which activity of one reaction implies activity of another reaction. Several approaches for FCA have been proposed in the literature. Results: We introduce a new FCA algorithm, FFCA (Feasibility-based Flux Coupling Analysis), which is based on checking the feasibility of a system of linear inequalities. We show on a set of benchmarks that for genome-scale networks FFCA is faster than other existing FCA methods. Conclusions: We present FFCA as a new method for flux coupling analysis and prove it to be faster than existing approaches. A corresponding software tool is freely available for non-commercial use at http://www.bioinformatics.org/ffca/. Y1 - 2011 U6 - https://doi.org/10.1186/1471-2105-12-236 SN - 1471-2105 VL - 12 IS - 12 PB - BioMed Central CY - London ER - TY - JOUR A1 - Schudoma, Christian A1 - Larhlimi, Abdelhalim A1 - Walther, Dirk T1 - The influence of the local sequence environment on RNA loop structures JF - RNA : a publication of the RNA Society N2 - RNA folding is assumed to be a hierarchical process. The secondary structure of an RNA molecule, signified by base-pairing and stacking interactions between the paired bases, is formed first. Subsequently, the RNA molecule adopts an energetically favorable three-dimensional conformation in the structural space determined mainly by the rotational degrees of freedom associated with the backbone of regions of unpaired nucleotides (loops). To what extent the backbone conformation of RNA loops also results from interactions within the local sequence context or rather follows global optimization constraints alone has not been addressed yet. Because the majority of base stacking interactions are exerted locally, a critical influence of local sequence on local structure appears plausible. Thus, local loop structure ought to be predictable, at least in part, from the local sequence context alone. To test this hypothesis, we used Random Forests on a nonredundant data set of unpaired nucleotides extracted from 97 X-ray structures from the Protein Data Bank (PDB) to predict discrete backbone angle conformations given by the discretized eta/theta-pseudo-torsional space. Predictions on balanced sets with four to six conformational classes using local sequence information yielded average accuracies of up to 55%, thus significantly better than expected by chance (17%-25%). Bases close to the central nucleotide appear to be most tightly linked to its conformation. Our results suggest that RNA loop structure does not only depend on long-range base-pairing interactions; instead, it appears that local sequence context exerts a significant influence on the formation of the local loop structure. KW - RNA KW - 3D structure KW - structure prediction KW - Random Forests KW - machine learning KW - backbone conformation Y1 - 2011 U6 - https://doi.org/10.1261/rna.2550211 SN - 1355-8382 VL - 17 IS - 7 SP - 1247 EP - 1257 PB - Cold Spring Harbor Laboratory Press CY - Cold Spring Harbor, NY ER - TY - JOUR A1 - Höhenwarter, Wolfgang A1 - Larhlimi, Abdelhalim A1 - Hummel, Jan A1 - Egelhofer, Volker A1 - Selbig, Joachim A1 - van Dongen, Joost T. A1 - Wienkoop, Stefanie A1 - Weckwerth, Wolfram T1 - MAPA Distinguishes genotype-specific variability of highly similar regulatory protein isoforms in potato tuber JF - Journal of proteome research N2 - Mass Accuracy Precursor Alignment is a fast and flexible method for comparative proteome analysis that allows the comparison of unprecedented numbers of shotgun proteomics analyses on a personal computer in a matter of hours. We compared 183 LC-MS analyses and more than 2 million MS/MS spectra and could define and separate the proteomic phenotypes of field grown tubers of 12 tetraploid cultivars of the crop plant Solanum tuberosum. Protein isoforms of patatin as well as other major gene families such as lipoxygenase and cysteine protease inhibitor that regulate tuber development were found to be the primary source of variability between the cultivars. This suggests that differentially expressed protein isoforms modulate genotype specific tuber development and the plant phenotype. We properly assigned the measured abundance of tryptic peptides to different protein isoforms that share extensive stretches of primary structure and thus inferred their abundance. Peptides unique to different protein isoforms were used to classify the remaining peptides assigned to the entire subset of isoforms based on a common abundance profile using multivariate statistical procedures. We identified nearly 4000,proteins which we used for quantitative functional annotation making this the most extensive study of the tuber proteome to date. KW - comparative proteomics KW - mass accuracy KW - protein isoforms KW - potato tuber KW - lipoxygenase KW - protease inhibitor KW - phenotype KW - genetic variability Y1 - 2011 U6 - https://doi.org/10.1021/pr101109a SN - 1535-3893 VL - 10 IS - 7 SP - 2979 EP - 2991 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Larhlimi, Abdelhalim A1 - Blachon, Sylvain A1 - Selbig, Joachim A1 - Nikoloski, Zoran T1 - Robustness of metabolic networks a review of existing definitions JF - Biosystems : journal of biological and information processing sciences N2 - Describing the determinants of robustness of biological systems has become one of the central questions in systems biology. Despite the increasing research efforts, it has proven difficult to arrive at a unifying definition for this important concept. We argue that this is due to the multifaceted nature of the concept of robustness and the possibility to formally capture it at different levels of systemic formalisms (e.g, topology and dynamic behavior). Here we provide a comprehensive review of the existing definitions of robustness pertaining to metabolic networks. As kinetic approaches have been excellently reviewed elsewhere, we focus on definitions of robustness proposed within graph-theoretic and constraint-based formalisms. KW - Robustness KW - Metabolic networks KW - Graph theory KW - Constraint-based approaches Y1 - 2011 U6 - https://doi.org/10.1016/j.biosystems.2011.06.002 SN - 0303-2647 VL - 106 IS - 1 SP - 1 EP - 8 PB - Elsevier CY - Oxford ER -