References of "Nature Methods"
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See detailWisdom of crowds for robust gene network inference
Marbach, Daniel; Costello, James C.; Küffner, Robert et al

in Nature Methods (2012), 9

Reconstructing gene regulatory networks from high-throughput data is a long-standing challenge. Through the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we performed a ... [more ▼]

Reconstructing gene regulatory networks from high-throughput data is a long-standing challenge. Through the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we performed a comprehensive blind assessment of over 30 network inference methods on Escherichia coli, Staphylococcus aureus, Saccharomyces cerevisiae and in silico microarray data. We characterize the performance, data requirements and inherent biases of different inference approaches, and we provide guidelines for algorithm application and development. We observed that no single inference method performs optimally across all data sets. In contrast, integration of predictions from multiple inference methods shows robust and high performance across diverse data sets. We thereby constructed high-confidence networks for E. coli and S. aureus, each comprising ~ 1,700 transcriptional interactions at a precision of ~50%. We experimentally tested 53 previously unobserved regulatory interactions in E. coli, of which 23 (43%) were supported. Our results establish community-based methods as a powerful and robust tool for the inference of transcriptional gene regulatory networks. [less ▲]

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See detailParallel detection of antigen-specific T-cell responses by multidimensional encoding of peptide-Major Histocompatibility Complexes
Reker Hadrup, Sine; Bakker, Arnold H; Shu, Chengyi J. et al

in Nature Methods (2009), 6((7)), 520-526

Abstract The use of fluorescently labeled MHC multimers has become an essential technique for the analysis of disease- and therapy-induced T cell immunity. While classical MHC multimer analyses are well ... [more ▼]

Abstract The use of fluorescently labeled MHC multimers has become an essential technique for the analysis of disease- and therapy-induced T cell immunity. While classical MHC multimer analyses are well-suited for the detection of immune responses against a few epitopes, limitations on patient sample size preclude a comprehensive analysis of T cell immunity. To address this issue, we have developed a combinatorial encoding strategy that allows the parallel detection of a multitude of different T cell populations within a single sample. Detection of antigen-specific T cells from peripheral blood by combinatorial encoding is as efficient as detection with conventional PE labeled multimers, but results in a significantly increased sensitivity, and most importantly, allows comprehensive screens to be performed on patient material. Proof of principle for the feasibility of large-scale screening of patient material was obtained by analysis of HLA-A3 restricted T cell responses against known and potential melanoma-associated antigens in peripheral blood from melanoma patients. 2 [less ▲]

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See detail'Edgetic' perturbation of a C. elegans BCL2 ortholog.
Dreze, Matija; Charloteaux, Benoît ULg; Milstein, Stuart et al

in Nature Methods (2009), 6(11), 843-9

Genes and gene products do not function in isolation but within highly interconnected 'interactome' networks, modeled as graphs of nodes and edges representing macromolecules and interactions between them ... [more ▼]

Genes and gene products do not function in isolation but within highly interconnected 'interactome' networks, modeled as graphs of nodes and edges representing macromolecules and interactions between them, respectively. We propose to investigate genotype-phenotype associations by methodical use of alleles that lack single interactions, while retaining all others, in contrast to genetic approaches designed to eliminate gene products completely. We describe an integrated strategy based on the reverse yeast two-hybrid system to isolate and characterize such edge-specific, or 'edgetic', alleles. We established a proof of concept with CED-9, a Caenorhabditis elegans BCL2 ortholog. Using ced-9 edgetic alleles, we uncovered a new potential functional link between apoptosis and a centrosomal protein. This approach is amenable to higher throughput and is particularly applicable to interactome network analysis in organisms for which transgenesis is straightforward. [less ▲]

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See detailModeling Lymphangiogenesis in a three-dimensional culture system
Bruyere, Françoise; Melen-Lamalle, Laurence; Blacher, Silvia ULg et al

in Nature Methods (2008), 5(5), 431-437

Unraveling the molecular mechanisms of lymphangiogenesis is hampered by the lack of appropriate in vitro models of three-dimensional (3D) lymph vessel growth which can be used to exploit the potential of ... [more ▼]

Unraveling the molecular mechanisms of lymphangiogenesis is hampered by the lack of appropriate in vitro models of three-dimensional (3D) lymph vessel growth which can be used to exploit the potential of available transgenic mice. We developed a potent reproducible and quantifiable 3D-culture system of lymphatic endothelial cells, the lymphatic ring assay, bridging the gap between 2D-in vitro and in vivo models of lymphangiogenesis. Mice thoracic duct fragments are embedded in a collagen gel leading to the formation of lymphatic capillaries containing a lumen as assessed by electron microscopy and immunostaining. This assay phenocopies the different steps of lymphangiogenesis, including the spreading from a preexisting vessel, cell proliferation, migration and differentiation into capillaries. Our study provides evidence for the implication of an individual matrix metalloproteinase, MMP-2, during lymphangiogenesis. The lymphatic ring assay is a robust, quantifiable and reproducible system which offers new opportunities for rapid identification of unknown regulators of lymphangiogenesis. [less ▲]

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