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Article

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

by
Julia Rechenberger
1,†,
Patroklos Samaras
1,†,
Anna Jarzab
1,
Juergen Behr
2,
Martin Frejno
1,
Ana Djukovic
3,
Jaime Sanz
4,5,
Eva M. González-Barberá
4,
Miguel Salavert
4,
Jose Luis López-Hontangas
4,
Karina B. Xavier
6,
Laurent Debrauwer
7,8,
Jean-Marc Rolain
9,
Miguel Sanz
4,5,
Marc Garcia-Garcera
10,
Mathias Wilhelm
1,*,
Carles Ubeda
3,11,* and
Bernhard Kuster
1,2,*
1
Chair of Proteomics and Bioanalytics, Technical University of Munich, 85354 Freising, Germany
2
Bavarian Center for Biomolecular Mass Spectrometry, Technical University of Munich, 85354 Freising, Germany
3
Centro Superior de Investigación en Salud Pública-FISABIO, 46020 Valencia, Spain
4
Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain
5
CIBERONC, Instituto Carlos III, 28029 Madrid, Spain
6
Instituto Gulbenkian de Ciência, 2780 Oeiras, Portugal
7
Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 31027 Toulouse, France
8
Axiom Platform, UMR 1331 Toxalim, MetaToul-MetaboHUB, National Infrastructure of Metabolomics and Fluxomics, 31027 Toulouse, France
9
Aix Marseille Univ, IRD, APHM, MEPHI, IHU-Méditerranée Infection, 13385 Marseille, France
10
Department of Fundamental Microbiology, University of Lausanne, 1015 Lausanne, Switzerland
11
Centers of Biomedical Research Network (CIBER) in Epidemiology and Public Health, 28029 Madrid, Spain
 
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*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Proteomes 2019, 7(1), 2; https://doi.org/10.3390/proteomes7010002
Received: 31 October 2018 / Revised: 20 December 2018 / Accepted: 3 January 2019 / Published: 8 January 2019
(This article belongs to the Special Issue Metaproteomics)
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Abstract

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. View Full-Text
Keywords: human gut microbiome; metaproteome; data analysis; mass spectrometry; proteomics; clinical proteomics; multi-omics; multidrug-resistant Enterobacteriaceae human gut microbiome; metaproteome; data analysis; mass spectrometry; proteomics; clinical proteomics; multi-omics; multidrug-resistant Enterobacteriaceae
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MDPI and ACS Style

Rechenberger, J.; Samaras, P.; Jarzab, A.; Behr, J.; Frejno, M.; Djukovic, A.; Sanz, J.; González-Barberá, E.M.; Salavert, M.; López-Hontangas, J.L.; Xavier, K.B.; Debrauwer, L.; Rolain, J.-M.; Sanz, M.; Garcia-Garcera, M.; Wilhelm, M.; Ubeda, C.; Kuster, B. Challenges in Clinical Metaproteomics Highlighted by the Analysis of Acute Leukemia Patients with Gut Colonization by Multidrug-Resistant Enterobacteriaceae. Proteomes 2019, 7, 2. https://doi.org/10.3390/proteomes7010002

AMA Style

Rechenberger J, Samaras P, Jarzab A, Behr J, Frejno M, Djukovic A, Sanz J, González-Barberá EM, Salavert M, López-Hontangas JL, Xavier KB, Debrauwer L, Rolain J-M, Sanz M, Garcia-Garcera M, Wilhelm M, Ubeda C, Kuster B. Challenges in Clinical Metaproteomics Highlighted by the Analysis of Acute Leukemia Patients with Gut Colonization by Multidrug-Resistant Enterobacteriaceae. Proteomes. 2019; 7(1):2. https://doi.org/10.3390/proteomes7010002

Chicago/Turabian Style

Rechenberger, Julia, Patroklos Samaras, Anna Jarzab, Juergen Behr, Martin Frejno, Ana Djukovic, Jaime Sanz, Eva M. González-Barberá, Miguel Salavert, Jose Luis López-Hontangas, Karina B. Xavier, Laurent Debrauwer, Jean-Marc Rolain, Miguel Sanz, Marc Garcia-Garcera, Mathias Wilhelm, Carles Ubeda, and Bernhard Kuster. 2019. "Challenges in Clinical Metaproteomics Highlighted by the Analysis of Acute Leukemia Patients with Gut Colonization by Multidrug-Resistant Enterobacteriaceae" Proteomes 7, no. 1: 2. https://doi.org/10.3390/proteomes7010002

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