Imaging and Molecular Annotation of Xenographs and Tumours (IMAXT): High throughput data and analysis infrastructure

Eduardo A González-Solares; Ali Dariush; Carlos González-Fernández; Aybüke Küpcü Yoldaş; Alireza Molaeinezhad; Mohammad Al Sa'd; Leigh Smith; Tristan Whitmarsh; Neil Millar; Nicholas Chornay; Ilaria Falciatori; Atefeh Fatemi; Daniel Goodwin; Laura Kuett; Claire M Mulvey; Marta Páez Ribes; Fatime Qosaj; Andrew Roth; Ignacio Vázquez-García; Spencer S Watson; Jonas Windhager; Samuel Aparicio; Bernd Bodenmiller; Ed Boyden; Carlos Caldas; Owen Harris; Sohrab P Shah; Simon Tavaré; CRUK IMAXT Grand Challenge Team; Dario Bressan; Gregory J Hannon; Nicholas A Walton

doi:10.1017/S2633903X23000090

Imaging and Molecular Annotation of Xenographs and Tumours (IMAXT): High throughput data and analysis infrastructure

Biol Imaging. 2023 Apr 14:3:e11. doi: 10.1017/S2633903X23000090. eCollection 2023.

Authors

Eduardo A González-Solares¹, Ali Dariush^{1

2}, Carlos González-Fernández¹, Aybüke Küpcü Yoldaş¹, Alireza Molaeinezhad¹, Mohammad Al Sa'd¹, Leigh Smith¹, Tristan Whitmarsh¹, Neil Millar¹, Nicholas Chornay¹, Ilaria Falciatori², Atefeh Fatemi², Daniel Goodwin^{3

4}, Laura Kuett^{5

6}, Claire M Mulvey², Marta Páez Ribes², Fatime Qosaj², Andrew Roth⁷, Ignacio Vázquez-García^{8

9}, Spencer S Watson¹⁰, Jonas Windhager^{5

6}, Samuel Aparicio¹¹, Bernd Bodenmiller^{5

6}, Ed Boyden^{3

4

12

13}, Carlos Caldas^{2

14}, Owen Harris¹⁵, Sohrab P Shah⁹, Simon Tavaré^{2

8

16}; CRUK IMAXT Grand Challenge Team; Dario Bressan², Gregory J Hannon², Nicholas A Walton¹

Affiliations

¹ Institute of Astronomy, University of Cambridge, Cambridge, United Kingdom.
² CRUK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, United Kingdom.
³ McGovern Institute, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴ McGovern Institute, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.
⁶ Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
⁷ Department of Computer Science, University of British Columbia, Vancouver, BC, Canada.
⁸ Herbert and Florence Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA.
⁹ Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁰ Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
¹¹ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
¹² Howard Hughes Medical Institute, Department of Physics, Harvard University, Cambridge, MA, USA.
¹³ Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
¹⁴ Cambridge Breast Unit, Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom.
¹⁵ Súil Interactive, Dublin, Ireland.
¹⁶ New York Genome Center, New York, NY, USA.

Abstract

With the aim of producing a 3D representation of tumors, imaging and molecular annotation of xenografts and tumors (IMAXT) uses a large variety of modalities in order to acquire tumor samples and produce a map of every cell in the tumor and its host environment. With the large volume and variety of data produced in the project, we developed automatic data workflows and analysis pipelines. We introduce a research methodology where scientists connect to a cloud environment to perform analysis close to where data are located, instead of bringing data to their local computers. Here, we present the data and analysis infrastructure, discuss the unique computational challenges and describe the analysis chains developed and deployed to generate molecularly annotated tumor models. Registration is achieved by use of a novel technique involving spherical fiducial marks that are visible in all imaging modalities used within IMAXT. The automatic pipelines are highly optimized and allow to obtain processed datasets several times quicker than current solutions narrowing the gap between data acquisition and scientific exploitation.

Keywords: Data management; data processing and analysis; fluorescence microscopy; imaging mass cytometry.