Project INF

Integrated database and standardised analysis of experimental data

High-throughput data play a key role in modern life sciences and systems biology by measuring the abundances or activities or all molecules in a biological system. Thus, these data allow researchers to identify important genes, transcripts or proteins. Moreover, the data are used in modeling approaches, which help to understand complex systems and create hypotheses. As the CRC/TR FungiNet focuses on novel concepts in infection biology, which combine systems biology modeling with basic and applied research, it extensively makes use of high-throughput data. One big challenge is the huge amount of data gathered by those experiments. The major aim of the information and infrastructure project (INF) is the storage, archiving, and standardized analyses of experimental high-throughput data from the CRC/TR FungiNet, and thus, to connect the experimental groups with the systems biology groups.

During the first funding period, INF implemented and applied pipelines for the standardized analysis of transcriptomics, proteomics, and genomics data, as well as for network modeling. Moreover, INF created metadata templates for in detail description of high-throughput experiments and their analysis. These pipelines and templates will be further updated and adapted in the second funding period.

For sharing of unstructured data and knowledge (SOPs, presentations, posters, models, etc.), INF manages the platform FungiNet-SEEK. In addition, INF established the data warehouse FungiNetDB to share and visualize of expression data, both within the CRC/TR FungiNet and the public.

The aim of the second funding period is to pre-process and upload all expression data of both fungal pathogens Aspergillus fumigatus and Candida albicans, and their hosts, to FungiNetDB and thus establish the data warehouse as a major resource for fungal gene expression data. Moreover, INF will establish another data warehouse for fungal and host-pathogen gene regulatory networks as a central repository for network models. Visualization of expression data in the networks will be achieved by coloring of nodes.

Principal Investigator
Publications
Author Year Title Journal Links
Heilig L, Natasha F, Trinks N, Aimanianda V, Wong SSW, Fontaine T, Terpitz U, Strobel L, Le Mauff F, Sheppard DC, Schäuble S, Kurzai O, Hünniger K, Weiss E, Vargas M, Howell PL, Panagiotou G, Wurster S, Einsele H, Loeffler J 2024 CD56-mediated activation of human natural killer cells is triggered by Aspergillus fumigatus galactosaminogalactan. PLoS Pathog. 20(6):e1012315 PubMed
Soll D, Chu CF, Sun S, Lutz V, Arunkumar M, Gachechiladze M, Schäuble S, Alissa-Alkhalaf M, Nguyen T, Khalil MA, Garcia-Ribelles I, Mueller M, Buder K, Michalke B, Panagiotou G, Ziegler-Martin K, Benz P, Schatzlmaier P, Hiller K, Stockinger H, Luu M, Schober K, Moosmann C, Schamel WW, Huber M, Zielinski CE 2024 Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity. Nat Immunol. PubMed
Garcia Lopez A, Albrecht-Eckardt D, Panagiotou G, Schäuble S 2024 FungiFun3: systemic gene set enrichment analysis for fungal species. Bioinformatics. 40(11) PubMed
Hedin KA, Mirhakkak MH, Vaaben TH, Sands C, Pedersen M, Baker A, Vazquez-Uribe R, Schäuble S, Panagiotou G, Wellejus A, Sommer MOA 2024 Saccharomyces boulardii enhances anti-inflammatory effectors and AhR activation via metabolic interactions in probiotic communities. ISME J. wrae212 PubMed
Sprague JL, Schille TB, Allert S, Trümper V, Lier A, Großmann P, Priest EL, Tsavou A, Panagiotou G, Naglik JR, Wilson D, Schäuble S, Kasper L, Hube B 2024 Candida albicans translocation through the intestinal epithelial barrier is promoted by fungal zinc acquisition and limited by NFκB-mediated barrier protection. PLoS Pathog. 20(3):e1012031 PubMed
Kelani AA, Bruch A, Rivieccio F, Visser C, Krueger T, Weaver D, Pan X, Schaeuble S, Panagiotou G, Kniemeyer O, Bromley MJ, Bowyer P, Barber AE, Brakhage AA, Blango MG. 2023 Disruption of the Aspergillus fumigatus RNA interference machinery alters the conidial transcriptome. RNA  [Epub ahead of print] PubMed
Brandt P, Mirhakkak MH, Wagner L, Driesch D, Möslinger A, Fänder P, Schäuble S, Panagiotou G, Vylkova S. 2023 High-Throughput Profiling of Candida auris Isolates Reveals Clade-Specific Metabolic Differences. Microbiol Spectrum : e0049823 PubMed
Seelbinder B, Lohinai Z, Vazquez-Uribe R, Brunke S, Chen X, Mirhakkak M, Lopez-Escalera S, Dome B, Megyesfalvi Z,  Berta J, Galffy G,  Dulka  E, Wellejus  A, Weiss GJ,  Bauer  M, Hube  B, Sommer MOA, Panagiotou  G 2023 Candida expansion in the gut of lung cancer patients associates with an ecological signature that supports growth under dysbiotic conditions. Nat Commun 14, 2673 Nature Commun
Häder, A, Schäuble, S, Gehlen, J, Thielemann N, Buerfent BC, Schüller V, Hess T, Wolf T, Schröer J, Weber M, Hünniger K, Löffler J, Vylkova S, Panagiotou G, Schumacher J, Kurzai O 2023 Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity. Nature Communications PubMed
Chao YY, Puhach A, Frieser D, Arunkumar M, Lehner L, Seeholzer T, Garcia-Lopez A, van der Wal M, Fibi-Smetana S, Dietschmann A, Sommermann T, Ćiković T, Taher L, Gresnigt MS, Vastert SJ, van Wijk F, Panagiotou G, Krappmann D, Groß O, Zielinski CE. 2023 Human TH17 cells engage gasdermin E pores to release IL-1α on NLRP3 inflammasome activation. Nat Immunol. 24(2):295-308 PubMed
Mirhakkak MH, Chen X, Ni Y, Heinekamp T, Sae-Ong T, Xu LL, Kurzai O, Barber AE, Brakhage AA, Boutin S, Schäuble S, Panagiotou G 2023 Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome. Nat Commun. 14(1):4369 PubMed
Schruefer S, Pschibul A, Wong SSW, Sae-Ong T, Wolf T, Schäuble S, Panagiotou G, Brakhage AA, Aimanianda V, Kniemeyer O, Ebel F 2023 Distinct transcriptional responses to fludioxonil in Aspergillus fumigatus and its ΔtcsC and Δskn7 mutants reveal a crucial role for Skn7 in the cell wall reorganizations triggered by this antifungal. BMC Genomics. 14;24(1):684 PubMed
Allert S, Schulz D, Kämmer P, Großmann P, Wolf T, Schäuble S, Panagiotou G, Brunke S, Hube B 2022 From environmental adaptation to host survival: Attributes that mediate pathogenicity of Candida auris. Virulence 13: 191-214. PubMed
Zoran T, Seelbinder B, White PL, Price JS, Kraus S, Kurzai O, Linde J, Häder A, Loeffler C, Grigoleit GU, Einsele H, Panagiotou G, Loeffler J, Schäuble S 2022 Molecular Profiling Reveals Characteristic and Decisive Signatures in Patients after Allogeneic Stem Cell Transplantation Suffering from Invasive Pulmonary Aspergillosis. J Fungi (Basel) 8(2):171 PubMed
Brandt P, Gerwien F, Wagner L, Krüger T, Ramirez-Zavala B, Mirhakkak MH, Schäuble S, Kniemeyer O, Panagiotou G, Brakhage AA, Morschhäuser J, Vylkova S 2022 Candida albicans SR-Like Protein Kinases Regulate Different Cellular Processes: Sky1 Is Involved in Control of Ion Homeostasis, While Sky2 Is Important for Dipeptide Utilization. Frontiers Cellular Infection Microbiology doi:0.3389/fcimb.2022.850531 Front. Cell. Infect. Microbiol.
Alonso-Roman R, Last A, Mirhakkak MH, Spraque JL, Möller L, Großmann P, Graf K, Gratz R, Mogavero S, Vylkova S, Panagiotou G, Schäuble S, Hube B, Gresnigt MS 2022 Lactobacillus rhamnosus colonisation antagonizes Candida albicans by forcing metabolic adaptations that compromise pathogenicity. Nat. Commun. 13, 3192 Nat. Commun.
Tappe B, Lauruschkat CD, Strobel L, Pantaleón García J, Kurzai O, Rebhan S, Kraus S, Pfeuffer-Jovic E, Bussemer L, Possler L, Held M, Hünniger K, Kniemeyer O, Schäuble S, Brakhage AA, Panagiotou G, White PL, Einsele H, Löffler J, Wurster S. 2022 COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds. Front Immunol. 13: 954985 PubMed
Patumcharoenpol P, Nakphaichit M, Panagiotou G, Senavonge A, Suratannon N, Vongsangnak W 2021 MetGEMs Toolbox: Metagenome-scale models as integrative toolbox for uncovering metabolic functions and routes of human gut microbiome. PLoS Computational Biology 17: e1008487 PubMed
Kämmer P, McNamara S, Wolf T, Conrad T, Allert S, Gerwien F, Hünniger K, Kurzai O, Guthke R, Hube B, Linde J, Brunke S 2021 Survival strategies of pathogenic Candida species in human blood show independent and specific adaptations. mBio 11: e02435-20 PubMed
Barber AE, Sae-Ong T, Kang K, Seelbinder B, Li J, Walther G, Panagiotou G, Kurzai O 2021 Aspergillus fumigatus pan-genome analysis identifies genetic variants associated with human infection. Nat Microbiol 6: 1526–36 PubMed
Çakır T, Panagiotou G, Uddin R, Durmuş S 2020 Novel approaches for Systems Biology of metabolism-oriented pathogen-human interactions: A mini-review. Front Cell Infect Microbiol 10: 52 (Review) Frontiers
Dissanayake TK, Schäuble S, Mirhakkak M, Wu WL, Ng ACK, Yip CCY, López AG, Yeung ML, Chan KH, Yuen KY, Panagiotou G, To KKW 2020 Comparative transcriptomic analysis of Rhinovirus and Influenza virus infection. Front Microbiol 11: 1580 PubMed
Seelbinder B, Chen J, Brunke S, Uribe RV, Meyer AC, de Oliveira Lino FS, Chan KF, Loos D, Imamovic L, Tsang CC, Lam RPK, Sridhar S, Kang K, Hube B, Woo PCY, Sommer MOA, Panagiotou G 2020 Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria. Microbiome 8: 133 Microbiome
Machata S, Müller MM, Lehmann R, Sieber S, Panagiotou G, Carvalho A, Cunha C, Lagrou K, Maertens J, Slevogt H, Jacobsen ID 2020 Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans. Virulence 11: 1337-51 Virulence
Kämmer P, McNamara S, Wolf T, Conrad T, Allert S, Gerwien F, Hünniger K, Kurzai O, Guthke R, Hube B, Linde J, Brunke S 2020 Survival strategies of pathogenic Candida species in human blood show independent and specific adaptations. mBio 11: e02435-20 PubMed
Seelbinder B, Wallstabe J, Marischen L, Weiss E, Wurster S, Page L, Löffler C, Bussemer L, Schmitt A, Wolf T, Becker J, Kalinke U, Vogel J, Panagiotou G, Einsele H, Westermann A, Schäuble S, Loeffler J 2020 RNA-seq reveals synergy in a human virus-fungus co-infection model. Cell Rep 33: 108389 PubMed
Khaliq W, Großmann P, Neugebauer S, Kleyman A, Domizi R, Calcinaro S, Brealey D, Gräler M, Kiehntopf M, Schäuble S, Singer M, Panagiotou G, Bauer M 2020 Lipid metabolic signatures deviate in sepsis survivors compared to non-survivors. Comput Struct Biotechnol J 18: 3678-3691 Science direct
Barber A, Riedel J, Sae-Ong T, Kang K, Brabetz W, Panagiotou G, Deising H, Kurzai O 2020 Effects of agricultural fungicide use on Aspergillus fumigatus abundance, antifungal susceptibility, and population structure. mBio 11: e02213-20 PubMed
Zoran T, Weber M, Springer J, White L, Bauer J, Schober A, Löffler C, Seelbinder B, Hünniger K, Kurzai O, Scherag A, Schäuble S, Morton CO, Einsele H, Linde J, Löffler J 2019 Treatment with etanercept and low monocyte concentration contribute to the risk of invasive aspergillosis in patients post allogeneic stem cell transplantation. Sci Rep 9: 17231 PubMed
Zheng T, Li J, Ni Y, Kang K, Misiakou MA, Imamovic L, Chow BKC, Rode AA, Bytzer P, Sommer M, Panagiotou P 2019 Mining, analyzing and integrating viral signals from metagenomic data. Microbiome 7: 42 PubMed
Vlaic S, Conrad T, Tokarski-Schnelle C, Gustafsson M, Dahmen U, Reinhard Guthke R, Schuster S 2018 ModuleDiscoverer: Identification of regulatory modules in protein-protein interaction networks. Sci Rep 8: 433 PubMed
Sieber P, Voigt K, Kämmer P, Brunke S, Schuster S, Linde L 2018 Comparative study on alternative splicing in human fungal pathogens suggests its involvement during host invasion. Front Microbiol 9: 2313 Front Microbiol
Conrad T, Kniemeyer O, Henkel SG, Krüger T, Mattern DJ, Valiante V, Guthke R, Jacobsen ID, Brakhage AA, Vlaic S, Linde J 2018 Module-detection approaches for the integration of multilevel omics data highlight the comprehensive response of Aspergillus fumigatus to caspofungin. BMC Syst Biol 12: 88 PubMed
Dix A, Czakai K, Leonhardt I, Schäferhoff K, Bonin M, Guthke R, Einsele H, Kurzai O, Löffler J, Linde J 2017 Specific and novel microRNAs are regulated as response to fungal infection in human dendritic cells. Front Microbiol 8: 270 PubMed
Wolf T, Kämmer P, Brunke S, Linde J 2017 Two's company: Studying interspecies relationships with dual RNA-seq. Curr Opin Microbiol 42: 7-12 (Review) PubMed
Magnusson R, Mariotti GP, Köpsén M, Lövfors W, Gawel DR, Jörnsten R, Linde J, Nordling TEM, Nyman E, Schulze S, Nestor CE, Zhang H, Cedersund G, Benson M, Tjärnberg A, Gustafsson M 2017 LASSIM-A network inference toolbox for genome-wide mechanistic modeling. PLoS Comput Biol 13: e1005608 PubMed
Durmuş S, Çakır T, Guthke R 2016 Editorial: Computational systems biology of pathogen-host interactions. Front Microbiol 7: 21 PubMed
Böhringer M, Pohlers S, Schulze S, Albrecht-Eckardt D, Piegsa J, Weber M, Martin R, Hünniger K, Linde J, Guthke R, Kurzai O 2016 Candida albicans infection leads to barrier breakdown and a MAPK/NF-κB mediated stress response in the intestinal epithelial cell line C2BBe1. Cell Microbiol 18: 889-904 Cell Microbiol
Dix A, Czakai K, Springer J, Fliesser M, Bonin M, Guthke R, Schmitt AL, Einsele H, Linde J, Löffler J 2016 Genome-wide expression profiling reveals S100B as biomarker for invasive Aspergillosis. Front Microbiol 7: 320 PubMed
Dix A, Vlaic S, Guthke R, Linde J 2016 Use of systems biology to decipher host-microbial interaction networks and predict biomarkers. Clin Microbiol Infect 22: 600-6 PubMed
Guthke R, Gerber S, Conrad T, Vlaic S, Durmuş S, Çakır T, Sevilgen FE, Shelest E, Linde J 2016 Data-based reconstruction of gene regulatory networks of fungal pathogens. Front Microbiol 7: 570 PubMed
Schulze S, Schleicher J, Guthke R, Linde J 2016 How to predict molecular interactions between species? Front Microbiol 7: 442 PubMed
Czakai K, Leonhardt I, Dix A, Bonin M, Linde J, Einsele H, Kurzai O, Loeffler J 2016 Krüppel-like Factor 4 modulates interleukin-6 release in human dendritic cells after in vitro stimulation with Aspergillus fumigatus and Candida albicans Sci Rep 6: 27990 PubMed
Horn F, Linde J, Mattern DJ, Walther G, Guthke R, Scherlach K, Martin K, Brakhage AA, Petzke L, Valiante V 2016 Draft genome sequences of fungus Aspergillus calidoustus. Genome Announc 4: e00102-16 PubMed
Hebecker B, Vlaic S, Conrad T, Bauer M, Brunke S, Kapitan M, Linde J, Hube B, Jacobsen ID 2016 Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions. Sci Rep 6: 36055 PubMed
Gerwien F, Safyan A, Wisgott S, Hille F, Kaemmer P, Linde J, Brunke S, Kasper L, Hube B 2016 A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts. mBio 7: e01782-16 PubMed
Schulze S, Henkel SG, Driesch D, Guthke R, Linde J 2015 Computational prediction of molecular pathogen-host interactions based on dual transcriptome data. Front Microbiol 6: 65 PubMed
Dix A, Hünniger K, Weber M, Guthke R, Kurzai O, Linde J 2015 Biomarker-based classification of bacterial and fungal whole-blood infections in a genome-wide expression study. Front Microbiol 6: 171 PubMed
Linde J, Schulze S, Henkel SG, Guthke R 2015 Data- and knowledge-based modeling of gene regulatory networks: An update. EXCLI J 14: 346-78 EXCLI Journal
Linde J, Duggan S, Weber M, Horn F, Sieber P, Hellwig D, Riege K, Marz M, Martin R, Guthke R, Kurzai O 2015 Defining the transcriptomic landscape of Candida glabrata by RNA-Seq. Nucleic Acids Res 43: 1392-406 PubMed
Priebe S, Kreisel C, Horn F, Guthke R, Linde J 2015 FungiFun2: a comprehensive online resource for systematic analysis of gene lists from fungal species. Bioinformatics 31: 445-6 PubMed
Horn F, Üzüm Z, Möbius N, Guthke R, Linde J, Hertweck C 2015 Draft genome sequences of symbiotic and nonsymbiotic Rhizopus microsporus Strains CBS 344.29 and ATCC 62417. Genome Announc 3: e01370-14 PubMed
Horn F, Habel A, Scharf DH, Dworschak J, Brakhage AA, Guthke R, Hertweck C, Linde J 2015 Draft genome sequence and gene annotation of the entomopathogenic fungus Verticillium hemipterigenum. Genome Announc 3: e01439-14 PubMed
Durmuş S, Çakır T, Özgür A, Guthke R 2015 A review on computational systems biology of pathogen-host interactions. Front Microbiol 6: 235 PubMed
Altwasser R, Baldin C, Weber J, Guthke R, Kniemeyer O, Brakhage AA, Linde J, Valiante V 2015 Network modeling reveals cross talk of MAP kinases during adaptation to caspofungin stress in Aspergillus fumigatus. PLoS One 10: e0136932 PubMed
Horn F, Linde J, Mattern DJ, Walther G, Guthke R, Brakhage AA, Valiante V 2015 Draft genome sequence of the fungus Penicillium brasilianum MG11. Genome Announc 3: e00724-15 PubMed
Schleicher J, Conrad T, Gustafsson M, Cedersund G, Guthke R, Linde J 2015 Facing the challenges of multiscale modelling of bacterial and fungal pathogen-host interactions. Brief Funct Genomics 16: 57-69 PubMed
Hillmann F, Linde J, Beckmann N, Cyrulies M, Strassburger M, Heinekamp T, Haas H, Guthke R, Kniemeyer O, Brakhage AA 2014 The novel globin protein fungoglobin is involved in low oxygen adaptation of Aspergillus fumigatus. Mol Microbiol 93: 539-53 PubMed
Horn F, Schroeckh V, Netzker T, Guthke R, Brakhage AA, Linde J 2014 Draft genome sequence of Streptomyces iranensis. Genome Announc 2: e00616-14 PubMed
Linde J, Schwartze V, Binder U, Lass-Flörl C, Voigt K, Horn F 2014 De Novo whole-genome sequence and genome annotation of Lichtheimia ramosa. Genome Announc 2: e00888-14 PubMed
Wartenberg A, Linde J, Martin R, Schreiner M, Horn F, Jacobsen ID, Jenull S, Wolf T, Kuchler K, Guthke R, Kurzai O, Forche A, d'Enfert C, Brunke S, Hube B 2014 Microevolution of Candida albicans in macrophages restores filamentation in a nonfilamentous mutant. PLoS Genet 10: e1004824 PubMed