Abstract (Expand)

In the emerging field of systems biology of fungal infection, one of the central roles belongs to the modeling of gene regulatory networks (GRNs). Utilizing omics-data, GRNs can be predicted by mathematical modeling. Here, we review current advances of data-based reconstruction of both small-scale and large-scale GRNs for human pathogenic fungi. The advantage of large-scale genome-wide modeling is the possibility to predict central (hub) genes and thereby indicate potential biomarkers and drug targets. In contrast, small-scale GRN models provide hypotheses on the mode of gene regulatory interactions, which have to be validated experimentally. Due to the lack of sufficient quantity and quality of both experimental data and prior knowledge about regulator-target gene relations, the genome-wide modeling still remains problematic for fungal pathogens. While a first genome-wide GRN model has already been published for Candida albicans, the feasibility of such modeling for Aspergillus fumigatus is evaluated in the present article. Based on this evaluation, opinions are drawn on future directions of GRN modeling of fungal pathogens. The crucial point of genome-wide GRN modeling is the experimental evidence, both used for inferring the networks (omics 'first-hand' data as well as literature data used as prior knowledge) and for validation and evaluation of the inferred network models.

Authors: Reinhard Guthke, S. Gerber, Theresia Conrad, S. Vlaic, S. Durmus, T. Cakir, F. E. Sevilgen, Ekaterina Shelest, Jörg Linde

Date Published: 22nd Apr 2016

Journal: Front Microbiol

Abstract (Expand)

Here, we report the draft genome sequence of Aspergillus calidoustus (strain SF006504). The functional annotation of A. calidoustus predicts a relatively large number of secondary metabolite gene clusters. The presented genome sequence builds the basis for further genome mining.

Authors: F. Horn, Jörg Linde, D. J. Mattern, G. Walther, Reinhard Guthke, K. Scherlach, K. Martin, Axel Brakhage, L. Petzke, Vito Valiante

Date Published: 12th Mar 2016

Journal: Genome Announc

Abstract (Expand)

The genus Penicillium belongs to the phylum Ascomycota and includes a variety of fungal species important for food and drug production. We report the draft genome sequence of Penicillium brasilianum MG11. This strain was isolated from soil, and it was reported to produce different secondary metabolites.

Authors: F. Horn, Jörg Linde, D. J. Mattern, G. Walther, Reinhard Guthke, Axel Brakhage, V. Valiante

Date Published: 5th Sep 2015

Journal: Genome Announc

Abstract (Expand)

Gene regulatory network inference is a systems biology approach which predicts interactions between genes with the help of high-throughput data. In this review, we present current and updated network inference methods focusing on novel techniques for data acquisition, network inference assessment, network inference for interacting species and the integration of prior knowledge. After the advance of Next-Generation-Sequencing of cDNAs derived from RNA samples (RNA-Seq) we discuss in detail its application to network inference. Furthermore, we present progress for large-scale or even full-genomic network inference as well as for small-scale condensed network inference and review advances in the evaluation of network inference methods by crowdsourcing. Finally, we reflect the current availability of data and prior knowledge sources and give an outlook for the inference of gene regulatory networks that reflect interacting species, in particular pathogen-host interactions.

Authors: Jörg Linde, Sylvie Schulze, S. G. Henkel, Reinhard Guthke

Date Published: 2nd Mar 2015

Journal: EXCLI J

Abstract (Expand)

Verticillium hemipterigenum (anamorph Torrubiella hemipterigena) is an entomopathogenic fungus and produces a broad range of secondary metabolites. Here, we present the draft genome sequence of the fungus, including gene structure and functional annotation. Genes were predicted incorporating RNA-Seq data and functionally annotated to provide the basis for further genome studies.

Authors: F. Horn, A. Habel, D. H. Scharf, J. Dworschak, Axel Brakhage, Reinhard Guthke, C. Hertweck, Jörg Linde

Date Published: 24th Jan 2015

Journal: Genome Announc

Abstract (Expand)

Candida glabrata is the second most common pathogenic Candida species and has emerged as a leading cause of nosocomial fungal infections. Its reduced susceptibility to antifungal drugs and its close relationship to Saccharomyces cerevisiae make it an interesting research focus. Although its genome sequence was published in 2004, little is known about its transcriptional dynamics. Here, we provide a detailed RNA-Seq-based analysis of the transcriptomic landscape of C. glabrata in nutrient-rich media, as well as under nitrosative stress and during pH shift. Using RNA-Seq data together with state-of-the-art gene prediction tools, we refined the annotation of the C. glabrata genome and predicted 49 novel protein-coding genes. Of these novel genes, 14 have homologs in S. cerevisiae and six are shared with other Candida species. We experimentally validated four novel protein-coding genes of which two are differentially regulated during pH shift and interaction with human neutrophils, indicating a potential role in host-pathogen interaction. Furthermore, we identified 58 novel non-protein-coding genes, 38 new introns and condition-specific alternative splicing. Finally, our data suggest different patterns of adaptation to pH shift and nitrosative stress in C. glabrata, Candida albicans and S. cerevisiae and thus further underline a distinct evolution of virulence in yeast.

Authors: Jörg Linde, S. Duggan, M. Weber, F. Horn, Patricia Sieber, D. Hellwig, Konstantin Riege, Manja Marz, R. Martin, Reinhard Guthke, Oliver Kurzai

Date Published: 13th Jan 2015

Journal: Nucleic Acids Res

Abstract (Expand)

Streptomyces iranensis HM 35 has been shown to exhibit 72.7% DNA-DNA similarity to the important drug rapamycin (sirolimus)-producing Streptomyces rapamycinicus NRRL5491. Here, we report the genome sequence of HM 35, which represents a partially overlapping repertoire of secondary metabolite gene clusters with S. rapamycinicus, including the gene cluster for rapamycin biosynthesis.

Authors: F. Horn, V. Schroeckh, T. Netzker, Reinhard Guthke, Axel Brakhage, Jörg Linde

Date Published: 19th Jul 2014

Journal: Genome Announc

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