COST is an intergovernmental framework for European Cooperation in Science and Technology, allowing the coordination of nationally-funded research on a European level. COST enables European researchers to jointly develop their research ideas and new initiatives across all scientific disciplines through trans-European networking of nationally funded research activities. Through supporting cooperation COST contributes to synergizing European research investments and opening the European Research Area to worldwide cooperation.

During the ASMS Sanibel conference on MSI in January 2007 a discussion began concerning the merits of a database of sample preparation protocols to enable MSI best-practice and aid new researchers entering the field. The problem of a lack of standardization and training in MSI was compellingly confirmed during the first  NordForsk funded MSI training course (organized by Corthals, McDonnell and Heeren and held at the FOM Institute AMOLF in March 2009): despite most participants using the same commercial matrix deposition device its practical usage differed widely (and in most cases contrary to the manufacturer’s recommendations). With suitable training all participants were able to generate near identical, high quality MSI datasets.

A similar situation was evident in the subsequent data analysis training course (organized by Corthals and McDonnell and  NordForsk funded, at Turku Centre for Biotechnology in December 2009). The majority of participants were restricted to the data analysis tools included in the software provided with their commercial instruments or the freely available Biomap software, an independent package developed for MSI by Markus Stoeckli (and which has been an essential element in its rapid uptake and development). Nevertheless the single biggest impediment to effective data analysis was a lack of training to fully utilize the statistical methods that were available. Following the training course the participants were able to generate robust classifiers and perform molecular histology much more effectively.

The restriction to data analysis packages supplied with the commercial mass spectrometers or Biomap means that most researchers have not been able to exploit the improved data analysis capabilities reported by data analysis specialists. A lack of a common data format standard is one significant reason most newly reported capabilities have not been utilized as much as they may otherwise be; an open-source MSI data analysis platform that incorporates the latest algorithms would certainly help but would only be part of the answer: the researchers must understand the data analysis algorithms in order to use them correctly. The lengthy introduction to MSI data analysis reported by Jones et al. was written to begin to address this need.

Only with sufficient training and co-operation can the full potential of MSI be utilized to test the capabilities of these highly cross-disciplinary tools against an array of diseases of present day concern, both in terms of improved diagnosis and pharmacological development. Central to this purpose will be the dissemination of the complementary techniques and expertise developed in independent research laboratories and their sustained interaction. Interaction between MSI researchers is crucial for devising best-practice guidelines and web-based experimental resources; the involvement of healthcare researchers is essential to ensure MSI targets real needs in healthcare research and pharmaceutical development.

In 2010 an application was made for a COST Action research network, to explicitly fund the cooperation needed to devise best practice guidelines in MSI, identify synergies in current MSI methods, and improve the accessibility of the technique by providing detailed training courses and opportunities for short term placements in Europe’s leading MSI laboratories. The first application was unsuccessful, falling at the final fence, but encouragingly we were invited to reapply the next year. The 2011 application was successful; one of just four COST Actions awarded out of more than one hundred applications, and will now run until November 2015.

COST Action BM1104, entitled “Mass Spectrometry Imaging: New Tools for Healthcare Research” involves all major European pharmaceutical companies and is supported by the MS vendors and the European Proteomics Association, which has made MSI one of four special initiatives. The central idea behind the COST Action is information exchange and training; for data acquisition, data analysis, and their application and to provide this knowledge as a public resource. The COST Action proposal (the Memorandum of Understanding) can be downloaded  here.

Data Acquisition – Best Practice Guidelines
Imaging MS requires the localized extraction of the molecules of interest followed by spatially correlated mass analysis. The sample preparation and mass analysis methods are critical factors that determine which molecules are measured, and the sensitivity and resolution at which they can be detected. Imaging MS and healthcare researchers will visit each other’s laboratories to test the performance of the imaging MS methods (sample preparation, mass analysis) that have been developed in each laboratory. The explicit inclusion of multiple pathologies and multiple practitioners provides the capacity and redundancy to begin devising best practice guidelines for multiple molecular classes and tissues.

Data Analysis
Histology-defined analysis can be used for the identification of biomarkers specific to pathological entities, and histology-independent analyses examine and classify the tissue solely on the basis of their MS signatures. Both of these approaches have the potential to generate new diagnostic tools and many data analysis techniques have been developed. However as most imaging MS experiments have been performed using commercial instruments using proprietary data formats, many clinical users have been ‘locked’ into single data analysis packages and have not been able to exploit the new data analysis capabilities. A new imaging data standard, imzML, was developed within the 6th framework program Computis. Substantial support from instrument vendors has led to imzML being implemented as an export option on most commercially available instruments. The different data analysis capabilities developed in the partner laboratories will be made imzML compliant to enable widespread data sharing and an explicit comparison of the different imaging data analysis tools. Comparing the performance of the data analysis tools for a variety of pathologies will establish standardized tools and context-dependent best-practice guidelines for analyzing such rich datasets.

An extensive programme of information exchange supplemented by Workshops and Training Courses, will be used to compare and contrast the methods that have developed in each individual laboratory. Supported Activities include:An extensive programme of information exchange supplemented by Workshops and Training Courses, will be used to compare and contrast the methods that have developed in each individual laboratory. Supported Activities include:

• Short-Term Scientific Missions enable young researchers to visit participating laboratories for upto 3 months at a time (minimum duration 1 week). Up to €2500 is available for each STSM, and the aim is to fund 12 places per year.
• Workshops enable in depth discussions of the topics of the Action, with particular attention given to the findings of the STSM’s. The number of COST supported places is dependent on the Workshop. COST support provides a generous travel allowance.
• Training Courses provide extensive theoretical and hands-on training in all aspects of MSI (data acquisition, data analysis and its application). Currently up to 10 COST stipends are available for each training course, for which the course is provided without cost and 500 Euro towards travel expenses.
• Management Committee meetings focus on the administration, policy and the future direction of the COST Action. Two MC members and two substitute MC members are allowed from each participating country.

Short-Term Scientific Missions and Workshops are organized by the  Work Group Chairs. For the training courses please contact the  local organizers or the Chair/Vice-Chair of the Action.

Working group 1: Best practice guidelines for imaging MS data aquisition
Chair:  Martina Marchetti-Deschmann (Austria), Co-Chair:  Isabelle Fournier (France)

Working group 2: Data analysis and data sharing
Chair:  Ron Heeren (The Netherlands), Co-Chair:  Andreas Römpp (Germany)

Working group 3: Application to topical diseases
Chair:  Garry Corthals (Finland), Co-Chair:  Per Andrén (Sweden)

Mass spectrometric imaging of in vivo protein and lipid adsorption on biodegradable vascular replacement systems.
Sophie M. Fröhlich, Magdalena Eilenberg, Anastasiya Svirkova, Christian Grasl, Robert Liska, Helga Bergmeister and Martina Marchetti-Deschmann
Analyst. 2015 Sep 7;140(17):6089-99.

Fabry disease: renal sphingolipid distribution in the α-Gal A knockout mouse model by mass spectrometric and immunohistochemical imaging.
Ladislav Kuchar, Helena Faltyskova, Lukas Krasny, Robert Dobrovolny, Helena Hulkova, Jana Ledvinova, Michael Volny, Martin Strohalm, Karel Lemr, Lenka Kryspinov1, Befekadu Asfaw, Jitka Rybová, Robert J. Desnick and Vladimir Havlicek
Anal Bioanal Chem. 2015 Mar; 407(8):2283-91. Epub 2014 Dec 27.

A MALDI-Mass Spectrometry Imaging method applicable to different formalin-fixed paraffin-embedded human tissues.
Gabriele De Sio, Andrew James Smith, Manuel Galli, Mattia Garancini, Clizia Chinello, Francesca Bono, Fabio Pagni and Fulvio Magni
Mol Biosyst. 2015 May 19;11(6):1507-14 Epub 2015 Jan 6.

MALDI-imaging mass spectrometry on tissues.
Veronica Mainini, Maciej Lalowski, Athanasios Gotsopoulos, Vasiliki Bitsika, Marc Baumann and Fulvio Magni
Methods Mol Biol. 2015; 1243:139-64

Imaging and identification of endogenous peptides from rat pituitary embedded in egg yolk.
Piotr Sosnowski, Tymoteusz Zera, Beata Wilenska, Ewa Szczepanska-Sadowska and Aleksandra Misicka
Rapid Communications in Mass Spectrometry (2015), 29 (4), 327–335.

Discussion point: reporting guidelines for mass spectrometry imaging.
Liam A. McDonnell, Andreas Römpp, Benjamin Balluff, Ron M. A. Heeren, Juan Pablo Albar, Per E. Andrén, Garry L. Corthals, Axel Walch and Markus Stoeckli
Anal Bioanal Chem. 2015 Mar;407(8):2035-45.

Spatial Segmentation of MALDI FT-ICR MSI Data: A Powerful Tool to Explore the Head and Neck Tumor In Situ Lipidome.
Lukas Krasny, Franziska Hoffmann, Günther Ernst, Dennis Trede, Theodore Alexandrov, Vladimir Havlicek, Orlando Guntinas-Lichius, Ferdinand von Eggeling and Anna C. Crecelius
J Am Soc Mass Spectrom. 2015 Jan; 26(1):36-43. Epub 2014 Nov 6.

Evaluation of Sparfloxacin Distribution by Mass Spectrometry Imaging in a Phototoxicity Model.
Stéphanie Marie Boudon, Grégory Morandi, Brendan Prideaux, Dieter Staab, Ursula Junker, Alex Odermatt, Markus Stoeckli and Daniel Bauer
J Am Soc Mass Spectrom. 2014 Oct;25(10):1803-9. Epub 2014 Jul 8.

Maldi-tof mass spectrometry imaging reveals molecular level changes in ultrahigh molecular weight polyethylene joint implants in correlation with lipid adsorption.
Sophie M. Fröhlich, Vasiliki-Maria Archodoulaki, Günter Allmaier, and Martina Marchetti-Deschmann
Anal Chem. 2014 Oct 7;86(19):9723-32. Epub 2014 Sep 25.

Synovial fluid protein adsorption on polymer-based artificial hip joint material investigated by MALDI-TOF mass spectrometry imaging
Sophie M. Fröhlich, Victoria Dorrer, Vasiliki-Maria Archodoulaki, Günter Allmaier and Martina Marchetti-Deschmann
EuPA Open Proteomics, Volume 4, September 2014, Pages 70–80.

30μm spatial resolution protein MALDI MSI: In-depth comparison of five sample preparation protocols applied to human healthy and atherosclerotic arteries.
Marta Martin-Lorenzo, Benjamin Balluff, Aroa Sanz-Maroto, René J.M. van Zeijl, Fernando Vivanco, Gloria Alvarez-Llamas and Liam A. McDonnell.
J Proteomics. 2014 Aug 28;108:465-8. Epub 2014 Jun 25.

Proteomics for the diagnosis of thyroid lesions: preliminary report.
F. Pagni, V. Mainini, M. Garancini, F. Bono, A. Vanzati, V. Giardini, M. Scardilli, P. Goffredo, A. J. Smith, M. Galli, G. De Sio, F. Magni
Cytopathology. 2015 Oct;26(5):318-24. Epub 2014 Jul 20.

iMatrixSpray: a free and open source sample preparation device for mass spectrometric imaging.
Markus Stoeckli, Dieter Staab, Michael Wetzel and Matthias Brechbuehl
Chimia (Aarau). March 2014;68(3):146-9.

MSiMass List: A Public Database of Identifications for Protein MALDI MS Imaging.
Liam A. McDonnell, Axel Walch, Markus Stoeckli and Garry L. Corthals
J Proteome Res. 2014 Feb 7;13(2):1138-42.

An Alternative Approach in Endocrine Pathology Research: MALDI-IMS in Papillary Thyroid Carcinoma
Veronica Mainini, Fabio Pagni , Mattia Garancini, Vittorio Giardini, Gabriele De Sio, Carlo Cusi, Cristina Arosio, Gaia Roversi, Clizia Chinello, Paola Caria, Roberta Vanni and Fulvio Magni.
Endocrine pathology. 2013 Dec;24(4):250-3.

MALDI imaging mass spectrometry in glomerulonephritis: feasibility study.
Veronica Mainini, Fabio Pagni, Franco Ferrario, Federico Pieruzzi, Marco Grasso, Andrea Stella, Giorgio Cattoretti and Fulvio Magni
Histopathology. 2013 Nov 27.

Imaging mass spectrometry: a new tool for kidney disease investigations
Maciej Lalowski, Fulvio Magni, Veronica Mainini, Evanthia Monogioudi, Athanasios Gotsopoulos, Rabah Soliymani, Clizia Chinello and Marc Baumann
Nephrol Dial Transplant. 2013 Jul;28(7):1648-56.

Detection of high molecular weight proteins by MALDI imaging mass spectrometry.
Veronica Mainini, Giorgio Bovo, Clizia Chinello, Erica Gianazza, Marco Grasso, Giorgio Cattoretti and Fulvio Magni
Molecular Biosystems. 2013 Jun;9(6):1101-7.

Proteomics imaging and the kidney
Fulvio Magni, Maciej Lalowski, Veronica Mainini, Martina Marchetti-Deschmann, Clizia Chinello, Andrea Urbani and Marc Baumann
Journal of Nephrology. 2013 May-Jun;26(3):430-436.

Going forward: Increasing the accessibility of imaging mass spectrometry.
Liam A. McDonnell, Ron M.A. Heeren, Per E. Andrén, Markus Stoeckli and Garry L. Corthals
J Proteomics. 2012 Aug 30;75(16):5113-21.

29 STSMs have taken place. Participation of different countries in STSMs:

2012

1. Vasiliki Bitsika from Athens to Helsinki

2. Martina Marchetti-Deschmann from Vienna to Amsterdam/ Leiden

3. Diego Cobice from Edinburgh to Amsterdam

4. Marta Martin Lorenzo from Madrid to Leiden

5. Florian Marty from Zurich to Amsterdam

6. Karolina Skraskova from Prague to Basel

7. Ricardo Carreira from Leiden To Uppsala

8. Rima Ait Belkacem from Marseille to Uppsala

9. Tiffany Porter from Geneva to Amsterdam

10. Veronica Mainini from Milan to Stevenage

2013

1. Tim Dekker from Leiden to Munich

2. Joanna Cappell from Glasgow to Amsterdam

3. Na Sun from Munich to Leiden

4. Bram Heijs from Leiden to Sheffield

5. Anna Crecelius from Jena to Prague

6. Bianca Squillaci from Stevenage to Prague

7. Beata Willeńska from Warsaw To Vienna

8. Piotr Sosnowski from Warsaw to Vienna

9. Beatriz Rocha from La Coruña to Amsterdam

10. Marta Martin Lorenzo from Madrid to Leiden

11. Hermelindis Ruh from Mannheim to Stevenage

12. Maria Laura Dilillo from Pisa to Turku

 

2014

1. Matthew Gentry from Stevenage to Leiden

2. Marija Nisavic from Belgrade to Amsterdam

3. Heather Hulme from Glasgow to Uppsala

4. Anna Wojakowska from Gliwice to Sheffield

5. Shane Ellis from Amsterdam to Muenster

6. Ricardo Carreira from Leiden to Pisa

7. Rita Laires from Lisbon to Sheffield

Access the previous resources that were gathered and generated within the COST Action BM1104 and by MSIS.