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Challenges in Clinical Metaproteomics Highlighted by the Analysis of Acute Leukemia Patients with Gut Colonization by Multidrug-Resistant Enterobacteriaceae.

  • Rechenberger J Chair of Proteomics and Bioanalytics, Technical University of Munich, 85354 Freising, Germany. julia.rechenberger@tum.de.
  • Samaras P Chair of Proteomics and Bioanalytics, Technical University of Munich, 85354 Freising, Germany. patroklos.samaras@tum.de.
  • Jarzab A Chair of Proteomics and Bioanalytics, Technical University of Munich, 85354 Freising, Germany. anna.jarzab@tum.de.
  • Behr J Bavarian Center for Biomolecular Mass Spectrometry, Technical University of Munich, 85354 Freising, Germany. juergen.behr@tum.de.
  • Frejno M Chair of Proteomics and Bioanalytics, Technical University of Munich, 85354 Freising, Germany. martin.frejno@tum.de.
  • Djukovic A Centro Superior de Investigación en Salud Pública-FISABIO, 46020 Valencia, Spain. adjukovic@gmail.com.
  • Sanz J Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain. sanz_jai@gva.es.
  • González-Barberá EM Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain. evamariagonzalezbarbera@gmail.com.
  • Salavert M Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain. salavert_mig@gva.es.
  • López-Hontangas JL Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain. lopez_jlu@gva.es.
  • Xavier KB Instituto Gulbenkian de Ciência, 2780 Oeiras, Portugal. kxavier@igc.gulbenkian.pt.
  • Debrauwer L Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 31027 Toulouse, France. laurent.debrauwer@inra.fr.
  • Rolain JM Aix Marseille Univ, IRD, APHM, MEPHI, IHU-Méditerranée Infection, 13385 Marseille, France. jean-marc.rolain@univ-amu.fr.
  • Sanz M Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain. sanz_mig@gva.es.
  • Garcia-Garcera M Department of Fundamental Microbiology, University of Lausanne, 1015 Lausanne, Switzerland. marc.garcia.garcera@gmail.com.
  • Wilhelm M Chair of Proteomics and Bioanalytics, Technical University of Munich, 85354 Freising, Germany. mathias.wilhelm@tum.de.
  • Ubeda C Centro Superior de Investigación en Salud Pública-FISABIO, 46020 Valencia, Spain. ubeda_carmor@gva.es.
  • Kuster B Chair of Proteomics and Bioanalytics, Technical University of Munich, 85354 Freising, Germany. kuster@tum.de.
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  • 2019-01-11
Published in:
  • Proteomes. - 2019
clinical proteomics
data analysis
human gut microbiome
mass spectrometry
metaproteome
multi-omics
multidrug-resistant Enterobacteriaceae
proteomics
English The microbiome has a strong impact on human health and disease and is, therefore, increasingly studied in a clinical context. Metaproteomics is also attracting considerable attention, and such data can be efficiently generated today owing to improvements in mass spectrometry-based proteomics. As we will discuss in this study, there are still major challenges notably in data analysis that need to be overcome. Here, we analyzed 212 fecal samples from 56 hospitalized acute leukemia patients with multidrug-resistant Enterobactericeae (MRE) gut colonization using metagenomics and metaproteomics. This is one of the largest clinical metaproteomic studies to date, and the first metaproteomic study addressing the gut microbiome in MRE colonized acute leukemia patients. Based on this substantial data set, we discuss major current limitations in clinical metaproteomic data analysis to provide guidance to researchers in the field. Notably, the results show that public metagenome databases are incomplete and that sample-specific metagenomes improve results. Furthermore, biological variation is tremendous which challenges clinical study designs and argues that longitudinal measurements of individual patients are a valuable future addition to the analysis of patient cohorts.
Language
  • English
Open access status
gold
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Persistent URL
https://folia.unifr.ch/global/documents/295606
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