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2. How to Build the Virtual Cell with Artificial Intelligence: Priorities and Opportunities

Author

Bunne, Charlotte, Roohani, Yusuf, Rosen, Yanay, Gupta, Ankit, Zhang, Xikun, Roed, Marcel, Alexandrov, Theo, AlQuraishi, Mohammed, Brennan, Patricia, Burkhardt, Daniel B., Califano, Andrea, Cool, Jonah, Dernburg, Abby F., Ewing, Kirsty, Fox, Emily B., Haury, Matthias, Herr, Amy E., Horvitz, Eric, Hsu, Patrick D., Jain, Viren, Johnson, Gregory R., Kalil, Thomas, Kelley, David R., Kelley, Shana O., Kreshuk, Anna, Mitchison, Tim, Otte, Stephani, Shendure, Jay, Sofroniew, Nicholas J., Theis, Fabian, Theodoris, Christina V., Upadhyayula, Srigokul, Valer, Marc, Wang, Bo, Xing, Eric, Yeung-Levy, Serena, Zitnik, Marinka, Karaletsos, Theofanis, Regev, Aviv, Lundberg, Emma, Leskovec, Jure, and Quake, Stephen R.

Subjects
Quantitative Biology - Quantitative Methods, Computer Science - Artificial Intelligence, Computer Science - Machine Learning, Quantitative Biology - Neurons and Cognition
Abstract

The cell is arguably the most fundamental unit of life and is central to understanding biology. Accurate modeling of cells is important for this understanding as well as for determining the root causes of disease. Recent advances in artificial intelligence (AI), combined with the ability to generate large-scale experimental data, present novel opportunities to model cells. Here we propose a vision of leveraging advances in AI to construct virtual cells, high-fidelity simulations of cells and cellular systems under different conditions that are directly learned from biological data across measurements and scales. We discuss desired capabilities of such AI Virtual Cells, including generating universal representations of biological entities across scales, and facilitating interpretable in silico experiments to predict and understand their behavior using virtual instruments. We further address the challenges, opportunities and requirements to realize this vision including data needs, evaluation strategies, and community standards and engagement to ensure biological accuracy and broad utility. We envision a future where AI Virtual Cells help identify new drug targets, predict cellular responses to perturbations, as well as scale hypothesis exploration. With open science collaborations across the biomedical ecosystem that includes academia, philanthropy, and the biopharma and AI industries, a comprehensive predictive understanding of cell mechanisms and interactions has come into reach.

Published
2024

3. Enabling Global Image Data Sharing in the Life Sciences

Author

Bajcsy, Peter, Bhattiprolu, Sreenivas, Boerner, Katy, Cimini, Beth A, Collinson, Lucy, Ellenberg, Jan, Fiolka, Reto, Giger, Maryellen, Goscinski, Wojtek, Hartley, Matthew, Hotaling, Nathan, Horwitz, Rick, Jug, Florian, Kreshuk, Anna, Lundberg, Emma, Mathur, Aastha, Narayan, Kedar, Onami, Shuichi, Plant, Anne L., Prior, Fred, Swedlow, Jason, Taylor, Adam, and Keppler, Antje

Subjects
Quantitative Biology - Other Quantitative Biology
Abstract

Coordinated collaboration is essential to realize the added value of and infrastructure requirements for global image data sharing in the life sciences. In this White Paper, we take a first step at presenting some of the most common use cases as well as critical/emerging use cases of (including the use of artificial intelligence for) biological and medical image data, which would benefit tremendously from better frameworks for sharing (including technical, resourcing, legal, and ethical aspects). In the second half of this paper, we paint an ideal world scenario for how global image data sharing could work and benefit all life sciences and beyond. As this is still a long way off, we conclude by suggesting several concrete measures directed toward our institutions, existing imaging communities and data initiatives, and national funders, as well as publishers. Our vision is that within the next ten years, most researchers in the world will be able to make their datasets openly available and use quality image data of interest to them for their research and benefit. This paper is published in parallel with a companion White Paper entitled Harmonizing the Generation and Pre-publication Stewardship of FAIR Image Data, which addresses challenges and opportunities related to producing well-documented and high-quality image data that is ready to be shared. The driving goal is to address remaining challenges and democratize access to everyday practices and tools for a spectrum of biomedical researchers, regardless of their expertise, access to resources, and geographical location., Comment: This manuscript (arXiv:2401.13023) is published with a closely related companion entitled, Harmonizing the Generation and Pre-publication Stewardship of FAIR Image Data, which can be found at the following link, arXiv:2401.13022

Published
2024

4. Deep intravital brain tumor imaging enabled by tailored three-photon microscopy and analysis

Author

Schubert, Marc Cicero, Soyka, Stella Judith, Tamimi, Amr, Maus, Emanuel, Schroers, Julian, Wißmann, Niklas, Reyhan, Ekin, Tetzlaff, Svenja Kristin, Yang, Yvonne, Denninger, Robert, Peretzke, Robin, Beretta, Carlo, Drumm, Michael, Heuer, Alina, Buchert, Verena, Steffens, Alicia, Walshon, Jordain, McCortney, Kathleen, Heiland, Sabine, Bendszus, Martin, Neher, Peter, Golebiewska, Anna, Wick, Wolfgang, Winkler, Frank, Breckwoldt, Michael O., Kreshuk, Anna, Kuner, Thomas, Horbinski, Craig, Kurz, Felix Tobias, Prevedel, Robert, and Venkataramani, Varun

Published
2024
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5. Metrics reloaded: recommendations for image analysis validation

Author

Maier-Hein, Lena, Reinke, Annika, Godau, Patrick, Tizabi, Minu D., Buettner, Florian, Christodoulou, Evangelia, Glocker, Ben, Isensee, Fabian, Kleesiek, Jens, Kozubek, Michal, Reyes, Mauricio, Riegler, Michael A., Wiesenfarth, Manuel, Kavur, A. Emre, Sudre, Carole H., Baumgartner, Michael, Eisenmann, Matthias, Heckmann-Nötzel, Doreen, Rädsch, Tim, Acion, Laura, Antonelli, Michela, Arbel, Tal, Bakas, Spyridon, Benis, Arriel, Blaschko, Matthew B., Cardoso, M. Jorge, Cheplygina, Veronika, Cimini, Beth A., Collins, Gary S., Farahani, Keyvan, Ferrer, Luciana, Galdran, Adrian, van Ginneken, Bram, Haase, Robert, Hashimoto, Daniel A., Hoffman, Michael M., Huisman, Merel, Jannin, Pierre, Kahn, Charles E., Kainmueller, Dagmar, Kainz, Bernhard, Karargyris, Alexandros, Karthikesalingam, Alan, Kofler, Florian, Kopp-Schneider, Annette, Kreshuk, Anna, Kurc, Tahsin, Landman, Bennett A., Litjens, Geert, Madani, Amin, Maier-Hein, Klaus, Martel, Anne L., Mattson, Peter, Meijering, Erik, Menze, Bjoern, Moons, Karel G. M., Müller, Henning, Nichyporuk, Brennan, Nickel, Felix, Petersen, Jens, Rajpoot, Nasir, Rieke, Nicola, Saez-Rodriguez, Julio, Sánchez, Clara I., Shetty, Shravya, van Smeden, Maarten, Summers, Ronald M., Taha, Abdel A., Tiulpin, Aleksei, Tsaftaris, Sotirios A., Van Calster, Ben, Varoquaux, Gaël, and Jäger, Paul F.

Published
2024
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6. Understanding metric-related pitfalls in image analysis validation

Author

Reinke, Annika, Tizabi, Minu D., Baumgartner, Michael, Eisenmann, Matthias, Heckmann-Nötzel, Doreen, Kavur, A. Emre, Rädsch, Tim, Sudre, Carole H., Acion, Laura, Antonelli, Michela, Arbel, Tal, Bakas, Spyridon, Benis, Arriel, Buettner, Florian, Cardoso, M. Jorge, Cheplygina, Veronika, Chen, Jianxu, Christodoulou, Evangelia, Cimini, Beth A., Farahani, Keyvan, Ferrer, Luciana, Galdran, Adrian, van Ginneken, Bram, Glocker, Ben, Godau, Patrick, Hashimoto, Daniel A., Hoffman, Michael M., Huisman, Merel, Isensee, Fabian, Jannin, Pierre, Kahn, Charles E., Kainmueller, Dagmar, Kainz, Bernhard, Karargyris, Alexandros, Kleesiek, Jens, Kofler, Florian, Kooi, Thijs, Kopp-Schneider, Annette, Kozubek, Michal, Kreshuk, Anna, Kurc, Tahsin, Landman, Bennett A., Litjens, Geert, Madani, Amin, Maier-Hein, Klaus, Martel, Anne L., Meijering, Erik, Menze, Bjoern, Moons, Karel G. M., Müller, Henning, Nichyporuk, Brennan, Nickel, Felix, Petersen, Jens, Rafelski, Susanne M., Rajpoot, Nasir, Reyes, Mauricio, Riegler, Michael A., Rieke, Nicola, Saez-Rodriguez, Julio, Sánchez, Clara I., Shetty, Shravya, Summers, Ronald M., Taha, Abdel A., Tiulpin, Aleksei, Tsaftaris, Sotirios A., Van Calster, Ben, Varoquaux, Gaël, Yaniv, Ziv R., Jäger, Paul F., and Maier-Hein, Lena

Published
2024
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7. How to Build the Virtual Cell with Artificial Intelligence: Priorities and Opportunities.

Author

Charlotte Bunne, Yusuf Roohani, Yanay Rosen, Ankit Gupta, Xikun Zhang 0001, Marcel Roed, Theo Alexandrov, Mohammed AlQuraishi, Patricia Brennan, Daniel B. Burkhardt, Andrea Califano, Jonah Cool, Abby F. Dernburg, Kirsty Ewing, Emily B. Fox, Matthias Haury, Amy E. Herr, Eric Horvitz, Patrick D. Hsu, Viren Jain, Gregory R. Johnson, Thomas Kalil, David R. Kelley, Shana O. Kelley, Anna Kreshuk, Tim Mitchison, Stephani Otte, Jay Shendure, Nicolas J. Sofroniew, Fabian J. Theis, Christina V. Theodoris, Srigokul Upadhyayula, Marc Valer, Bo Wang 0044, Eric Xing, Serena Yeung-Levy, Marinka Zitnik, Theofanis Karaletsos, Aviv Regev, Emma Lundberg, Jure Leskovec, and Stephen R. Quake

Published
2024
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8. The crucial role of bioimage analysts in scientific research and publication.

Author

Cimini, Beth A., Bankhead, Peter, D'Antuono, Rocco, Fazeli, Elnaz, Fernandez-Rodriguez, Julia, Fuster-Barceló, Caterina, Haase, Robert, Jambor, Helena Klara, Jones, Martin L., Jug, Florian, Klemm, Anna H., Kreshuk, Anna, Marcotti, Stefania, Martins, Gabriel G., McArdle, Sara, Kota Miura, Muñoz-Barrutia, Arrate, Murphy, Laura C., Nelson, Michael S., and Nørrelykke, Simon F.

Subjects
SCIENTIFIC discoveries, QUANTITATIVE research, BIOLOGISTS, MICROSCOPY
Abstract

Bioimage analysis (BIA), a crucial discipline in biological research, overcomes the limitations of subjective analysis in microscopy through the creation and application of quantitative and reproducible methods. The establishment of dedicated BIA support within academic institutions is vital to improving research quality and efficiency and can significantly advance scientific discovery. However, a lack of training resources, limited career paths and insufficient recognition of the contributions made by bioimage analysts prevent the full realization of this potential. This Perspective -- the result of the recent The Company of Biologists Workshop 'Effectively Communicating Bioimage Analysis', which aimed to summarize the global BIA landscape, categorize obstacles and offer possible solutions -- proposes strategies to bring about a cultural shift towards recognizing the value of BIA by standardizing tools, improving training and encouraging formal credit for contributions. We also advocate for increased funding, standardized practices and enhanced collaboration, and we concludewith a call to action for all stakeholders to join efforts in advancing BIA. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Understanding metric-related pitfalls in image analysis validation

Author

Epi Methoden, Cancer, JC onderzoeksprogramma Methodology, Reinke, Annika, Tizabi, Minu D., Baumgartner, Michael, Eisenmann, Matthias, Heckmann-Nötzel, Doreen, Kavur, A. Emre, Rädsch, Tim, Sudre, Carole H., Acion, Laura, Antonelli, Michela, Arbel, Tal, Bakas, Spyridon, Benis, Arriel, Buettner, Florian, Cardoso, M. Jorge, Cheplygina, Veronika, Chen, Jianxu, Christodoulou, Evangelia, Cimini, Beth A., Farahani, Keyvan, Ferrer, Luciana, Galdran, Adrian, van Ginneken, Bram, Glocker, Ben, Godau, Patrick, Hashimoto, Daniel A., Hoffman, Michael M., Huisman, Merel, Isensee, Fabian, Jannin, Pierre, Kahn, Charles E., Kainmueller, Dagmar, Kainz, Bernhard, Karargyris, Alexandros, Kleesiek, Jens, Kofler, Florian, Kooi, Thijs, Kopp-Schneider, Annette, Kozubek, Michal, Kreshuk, Anna, Kurc, Tahsin, Landman, Bennett A., Litjens, Geert, Madani, Amin, Maier-Hein, Klaus, Martel, Anne L., Meijering, Erik, Menze, Bjoern, Moons, Karel G.M., Müller, Henning, Nichyporuk, Brennan, Nickel, Felix, Petersen, Jens, Rafelski, Susanne M., Rajpoot, Nasir, Reyes, Mauricio, Riegler, Michael A., Rieke, Nicola, Saez-Rodriguez, Julio, Sánchez, Clara I., Shetty, Shravya, Summers, Ronald M., Taha, Abdel A., Tiulpin, Aleksei, Tsaftaris, Sotirios A., Van Calster, Ben, Varoquaux, Gaël, Yaniv, Ziv R., Jäger, Paul F., Maier-Hein, Lena, Epi Methoden, Cancer, JC onderzoeksprogramma Methodology, Reinke, Annika, Tizabi, Minu D., Baumgartner, Michael, Eisenmann, Matthias, Heckmann-Nötzel, Doreen, Kavur, A. Emre, Rädsch, Tim, Sudre, Carole H., Acion, Laura, Antonelli, Michela, Arbel, Tal, Bakas, Spyridon, Benis, Arriel, Buettner, Florian, Cardoso, M. Jorge, Cheplygina, Veronika, Chen, Jianxu, Christodoulou, Evangelia, Cimini, Beth A., Farahani, Keyvan, Ferrer, Luciana, Galdran, Adrian, van Ginneken, Bram, Glocker, Ben, Godau, Patrick, Hashimoto, Daniel A., Hoffman, Michael M., Huisman, Merel, Isensee, Fabian, Jannin, Pierre, Kahn, Charles E., Kainmueller, Dagmar, Kainz, Bernhard, Karargyris, Alexandros, Kleesiek, Jens, Kofler, Florian, Kooi, Thijs, Kopp-Schneider, Annette, Kozubek, Michal, Kreshuk, Anna, Kurc, Tahsin, Landman, Bennett A., Litjens, Geert, Madani, Amin, Maier-Hein, Klaus, Martel, Anne L., Meijering, Erik, Menze, Bjoern, Moons, Karel G.M., Müller, Henning, Nichyporuk, Brennan, Nickel, Felix, Petersen, Jens, Rafelski, Susanne M., Rajpoot, Nasir, Reyes, Mauricio, Riegler, Michael A., Rieke, Nicola, Saez-Rodriguez, Julio, Sánchez, Clara I., Shetty, Shravya, Summers, Ronald M., Taha, Abdel A., Tiulpin, Aleksei, Tsaftaris, Sotirios A., Van Calster, Ben, Varoquaux, Gaël, Yaniv, Ziv R., Jäger, Paul F., and Maier-Hein, Lena

Published
2024

10. Metrics reloaded: recommendations for image analysis validation

Author

Epi Methoden, Cancer, JC onderzoeksprogramma Methodology, Infection & Immunity, Epi Methoden Team 3, Maier-Hein, Lena, Reinke, Annika, Godau, Patrick, Tizabi, Minu D., Buettner, Florian, Christodoulou, Evangelia, Glocker, Ben, Isensee, Fabian, Kleesiek, Jens, Kozubek, Michal, Reyes, Mauricio, Riegler, Michael A., Wiesenfarth, Manuel, Kavur, A. Emre, Sudre, Carole H., Baumgartner, Michael, Eisenmann, Matthias, Heckmann-Nötzel, Doreen, Rädsch, Tim, Acion, Laura, Antonelli, Michela, Arbel, Tal, Bakas, Spyridon, Benis, Arriel, Blaschko, Matthew B., Cardoso, M. Jorge, Cheplygina, Veronika, Cimini, Beth A., Collins, Gary S., Farahani, Keyvan, Ferrer, Luciana, Galdran, Adrian, van Ginneken, Bram, Haase, Robert, Hashimoto, Daniel A., Hoffman, Michael M., Huisman, Merel, Jannin, Pierre, Kahn, Charles E., Kainmueller, Dagmar, Kainz, Bernhard, Karargyris, Alexandros, Karthikesalingam, Alan, Kofler, Florian, Kopp-Schneider, Annette, Kreshuk, Anna, Kurc, Tahsin, Landman, Bennett A., Litjens, Geert, Madani, Amin, Maier-Hein, Klaus, Martel, Anne L., Mattson, Peter, Meijering, Erik, Menze, Bjoern, Moons, Karel G.M., Müller, Henning, Nichyporuk, Brennan, Nickel, Felix, Petersen, Jens, Rajpoot, Nasir, Rieke, Nicola, Saez-Rodriguez, Julio, Sánchez, Clara I., Shetty, Shravya, van Smeden, Maarten, Summers, Ronald M., Taha, Abdel A., Tiulpin, Aleksei, Tsaftaris, Sotirios A., Van Calster, Ben, Varoquaux, Gaël, Jäger, Paul F., Epi Methoden, Cancer, JC onderzoeksprogramma Methodology, Infection & Immunity, Epi Methoden Team 3, Maier-Hein, Lena, Reinke, Annika, Godau, Patrick, Tizabi, Minu D., Buettner, Florian, Christodoulou, Evangelia, Glocker, Ben, Isensee, Fabian, Kleesiek, Jens, Kozubek, Michal, Reyes, Mauricio, Riegler, Michael A., Wiesenfarth, Manuel, Kavur, A. Emre, Sudre, Carole H., Baumgartner, Michael, Eisenmann, Matthias, Heckmann-Nötzel, Doreen, Rädsch, Tim, Acion, Laura, Antonelli, Michela, Arbel, Tal, Bakas, Spyridon, Benis, Arriel, Blaschko, Matthew B., Cardoso, M. Jorge, Cheplygina, Veronika, Cimini, Beth A., Collins, Gary S., Farahani, Keyvan, Ferrer, Luciana, Galdran, Adrian, van Ginneken, Bram, Haase, Robert, Hashimoto, Daniel A., Hoffman, Michael M., Huisman, Merel, Jannin, Pierre, Kahn, Charles E., Kainmueller, Dagmar, Kainz, Bernhard, Karargyris, Alexandros, Karthikesalingam, Alan, Kofler, Florian, Kopp-Schneider, Annette, Kreshuk, Anna, Kurc, Tahsin, Landman, Bennett A., Litjens, Geert, Madani, Amin, Maier-Hein, Klaus, Martel, Anne L., Mattson, Peter, Meijering, Erik, Menze, Bjoern, Moons, Karel G.M., Müller, Henning, Nichyporuk, Brennan, Nickel, Felix, Petersen, Jens, Rajpoot, Nasir, Rieke, Nicola, Saez-Rodriguez, Julio, Sánchez, Clara I., Shetty, Shravya, van Smeden, Maarten, Summers, Ronald M., Taha, Abdel A., Tiulpin, Aleksei, Tsaftaris, Sotirios A., Van Calster, Ben, Varoquaux, Gaël, and Jäger, Paul F.

Published
2024

11. NFDI4BIOIMAGE - National Research Data Infrastructure for Microscopy and Bioimage Analysis

Author

Moore, J., Kunis, S., Grüning, B., Blank-Burian, M., Mallm, J.-P., Stöter, T., Zuschratter, W., Figge, M.T., Kreshuk, A., Tischer, C., Haase, R., Zobel, T., Bauer, P., Svensson, C.-M., Gerst, R., Hanne, J., Schmidt, C., Becker, M.M., Bocklitz, T., Bumberger, Jan, Chalopin, C., Chen, J., Czodrowski, P., Dickscheid, T., Fortmann-Grote, C., Huisken, J., Lohmann, J., Schauss, A., Baumann, M., Beretta, C., Burel, J.-M., Heuveline, V., Kuner, R., Landwehr, M., Leibfried, A., Nitschke, R., Mittal, D., von Suchodoletz, H., Valencia-Schneider, M., Zentis, P., Brilhaus, D., Hartley, M., Hülsmann, B., Dunker, Susanne, Keppler, A., Mathur, A., Meesters, C., Möbius, W., Nahnsen, S., Pfander, C., Rehwald, S., Serrano-Solano, B., Vilardell Scholten, L., Vogl, R., Becks, L., Ferrando-May, E., Weidtkamp-Peters, S., Moore, J., Kunis, S., Grüning, B., Blank-Burian, M., Mallm, J.-P., Stöter, T., Zuschratter, W., Figge, M.T., Kreshuk, A., Tischer, C., Haase, R., Zobel, T., Bauer, P., Svensson, C.-M., Gerst, R., Hanne, J., Schmidt, C., Becker, M.M., Bocklitz, T., Bumberger, Jan, Chalopin, C., Chen, J., Czodrowski, P., Dickscheid, T., Fortmann-Grote, C., Huisken, J., Lohmann, J., Schauss, A., Baumann, M., Beretta, C., Burel, J.-M., Heuveline, V., Kuner, R., Landwehr, M., Leibfried, A., Nitschke, R., Mittal, D., von Suchodoletz, H., Valencia-Schneider, M., Zentis, P., Brilhaus, D., Hartley, M., Hülsmann, B., Dunker, Susanne, Keppler, A., Mathur, A., Meesters, C., Möbius, W., Nahnsen, S., Pfander, C., Rehwald, S., Serrano-Solano, B., Vilardell Scholten, L., Vogl, R., Becks, L., Ferrando-May, E., and Weidtkamp-Peters, S.

Abstract

Bioimaging refers to a collection of methods to visualize the internal structures and mechanisms of living organisms. The fundamental tool, the microscope, has enabled seminal discoveries like that of the cell as the smallest unit of life, and continues to expand our understanding of biological processes. Today, we can follow the interaction of single molecules within nanoseconds in a living cell, and the development of complete small organisms like fish and flies over several days starting from the fertilized egg. Each image pixel encodes multiple spatiotemporal and spectral dimensions, compounding the massive volume and complexity of bioimage data. Proper handling of this data is indispensable for analysis and its lack has become a growing hindrance for the many disciplines of the life and biomedical sciences relying on bioimaging. No single domain has the expertise to tackle this bottleneck alone. As a method-specific consortium, NFDI4BIOMAGE seeks to address these issues, enabling bioimaging data to be shared and re-used like they are acquired, i.e., independently of disciplinary boundaries. We will provide solutions for exploiting the full information content of bioimage data and enable new discoveries through sharing and re-analysis. Our RDM strategy is based on a robust needs analysis that derives not only from a community survey but also from over a decade of experience in German BioImaging, the German Society for Microscopy and Image Analysis. It considers the entire lifecycle of bioimaging data, from acquisition to archiving, including analysis and enabling re-use. A foundational element of this strategy is the definition of a common, cloud-compatible, and interoperable digital object that bundles binary images with their descriptive and provenance metadata. With members from plant biology to neuroscience, NFDI4BIOIMAGE will champion the standardization of bioimage data to create a framework that answers discipline-specific needs while ensuring communicati

Published
2024

12. Metrics reloaded: recommendations for image analysis validation

Author

Maier-Hein, L., Reinke, A., Godau, P., Tizabi, M.D., Buettner, F., Christodoulou, E., Glocker, B., Isensee, F., Kleesiek, J., Kozubek, M., Reyes, M., Riegler, M.A., Wiesenfarth, M., Kavur, A.E., Sudre, C.H., Baumgartner, M., Eisenmann, M., Heckmann-Notzel, D., Radsch, T., Acion, L., Antonelli, M., Arbel, T., Bakas, S., Benis, A., Blaschko, M.B., Cardoso, M.J., Cheplygina, V., Cimini, B.A., Collins, G.S., Farahani, K., Ferrer, L., Galdran, A., Ginneken, B. van, Haase, R., Hashimoto, D.A., Hoffman, M.M., Huisman, M., Jannin, P., Kahn, C.E., Kainmueller, D., Kainz, B., Karargyris, A., Karthikesalingam, A., Kofler, F., Kopp-Schneider, A., Kreshuk, A., Kurc, T., Landman, B.A., Litjens, G.J., Madani, A., Maier-Hein, K., Martel, A.L., Mattson, P., Meijering, E., Menze, B., Moons, K.G., Muller, H., Nichyporuk, B., Nickel, F., Petersen, J., Rajpoot, N., Rieke, N., Saez-Rodriguez, J., Sanchez, C.I., Shetty, S., Smeden, M. van, Summers, R.M., Taha, A.A., Tiulpin, A., Tsaftaris, S.A., Calster, B. van, Varoquaux, G., Jager, P.F., Maier-Hein, L., Reinke, A., Godau, P., Tizabi, M.D., Buettner, F., Christodoulou, E., Glocker, B., Isensee, F., Kleesiek, J., Kozubek, M., Reyes, M., Riegler, M.A., Wiesenfarth, M., Kavur, A.E., Sudre, C.H., Baumgartner, M., Eisenmann, M., Heckmann-Notzel, D., Radsch, T., Acion, L., Antonelli, M., Arbel, T., Bakas, S., Benis, A., Blaschko, M.B., Cardoso, M.J., Cheplygina, V., Cimini, B.A., Collins, G.S., Farahani, K., Ferrer, L., Galdran, A., Ginneken, B. van, Haase, R., Hashimoto, D.A., Hoffman, M.M., Huisman, M., Jannin, P., Kahn, C.E., Kainmueller, D., Kainz, B., Karargyris, A., Karthikesalingam, A., Kofler, F., Kopp-Schneider, A., Kreshuk, A., Kurc, T., Landman, B.A., Litjens, G.J., Madani, A., Maier-Hein, K., Martel, A.L., Mattson, P., Meijering, E., Menze, B., Moons, K.G., Muller, H., Nichyporuk, B., Nickel, F., Petersen, J., Rajpoot, N., Rieke, N., Saez-Rodriguez, J., Sanchez, C.I., Shetty, S., Smeden, M. van, Summers, R.M., Taha, A.A., Tiulpin, A., Tsaftaris, S.A., Calster, B. van, Varoquaux, G., and Jager, P.F.

Abstract

Contains fulltext : 305368.pdf (Publisher’s version ) (Closed access), Increasing evidence shows that flaws in machine learning (ML) algorithm validation are an underestimated global problem. In biomedical image analysis, chosen performance metrics often do not reflect the domain interest, and thus fail to adequately measure scientific progress and hinder translation of ML techniques into practice. To overcome this, we created Metrics Reloaded, a comprehensive framework guiding researchers in the problem-aware selection of metrics. Developed by a large international consortium in a multistage Delphi process, it is based on the novel concept of a problem fingerprint-a structured representation of the given problem that captures all aspects that are relevant for metric selection, from the domain interest to the properties of the target structure(s), dataset and algorithm output. On the basis of the problem fingerprint, users are guided through the process of choosing and applying appropriate validation metrics while being made aware of potential pitfalls. Metrics Reloaded targets image analysis problems that can be interpreted as classification tasks at image, object or pixel level, namely image-level classification, object detection, semantic segmentation and instance segmentation tasks. To improve the user experience, we implemented the framework in the Metrics Reloaded online tool. Following the convergence of ML methodology across application domains, Metrics Reloaded fosters the convergence of validation methodology. Its applicability is demonstrated for various biomedical use cases.

Published
2024

13. Understanding metric-related pitfalls in image analysis validation

Author

Reinke, A., Tizabi, M.D., Baumgartner, M., Eisenmann, M., Heckmann-Notzel, D., Kavur, A.E., Radsch, T., Sudre, C.H., Acion, L., Antonelli, M., Arbel, T., Bakas, S., Benis, A., Buettner, F., Cardoso, M.J., Cheplygina, V., Chen, J., Christodoulou, E., Cimini, B.A., Farahani, K., Ferrer, L., Galdran, A., Ginneken, B. van, Glocker, B., Godau, P., Hashimoto, D.A., Hoffman, M.M., Huisman, M., Isensee, F., Jannin, P., Kahn, C.E., Kainmueller, D., Kainz, B., Karargyris, A., Kleesiek, J., Kofler, F., Kooi, T., Kopp-Schneider, A., Kozubek, M., Kreshuk, A., Kurc, T., Landman, B.A., Litjens, G.J., Madani, A., Maier-Hein, K., Martel, A.L., Meijering, E., Menze, B., Moons, K.G., Muller, H., Nichyporuk, B., Nickel, F., Petersen, J., Rafelski, S.M., Rajpoot, N., Reyes, M., Riegler, M.A., Rieke, N., Saez-Rodriguez, J., Sanchez, C.I., Shetty, S., Summers, R.M., Taha, A.A., Tiulpin, A., Tsaftaris, S.A., Calster, B. van, Varoquaux, G., Yaniv, Z.R., Jager, P.F., Maier-Hein, L., Reinke, A., Tizabi, M.D., Baumgartner, M., Eisenmann, M., Heckmann-Notzel, D., Kavur, A.E., Radsch, T., Sudre, C.H., Acion, L., Antonelli, M., Arbel, T., Bakas, S., Benis, A., Buettner, F., Cardoso, M.J., Cheplygina, V., Chen, J., Christodoulou, E., Cimini, B.A., Farahani, K., Ferrer, L., Galdran, A., Ginneken, B. van, Glocker, B., Godau, P., Hashimoto, D.A., Hoffman, M.M., Huisman, M., Isensee, F., Jannin, P., Kahn, C.E., Kainmueller, D., Kainz, B., Karargyris, A., Kleesiek, J., Kofler, F., Kooi, T., Kopp-Schneider, A., Kozubek, M., Kreshuk, A., Kurc, T., Landman, B.A., Litjens, G.J., Madani, A., Maier-Hein, K., Martel, A.L., Meijering, E., Menze, B., Moons, K.G., Muller, H., Nichyporuk, B., Nickel, F., Petersen, J., Rafelski, S.M., Rajpoot, N., Reyes, M., Riegler, M.A., Rieke, N., Saez-Rodriguez, J., Sanchez, C.I., Shetty, S., Summers, R.M., Taha, A.A., Tiulpin, A., Tsaftaris, S.A., Calster, B. van, Varoquaux, G., Yaniv, Z.R., Jager, P.F., and Maier-Hein, L.

Abstract

Contains fulltext : 305370.pdf (Publisher’s version ) (Closed access), Validation metrics are key for tracking scientific progress and bridging the current chasm between artificial intelligence research and its translation into practice. However, increasing evidence shows that, particularly in image analysis, metrics are often chosen inadequately. Although taking into account the individual strengths, weaknesses and limitations of validation metrics is a critical prerequisite to making educated choices, the relevant knowledge is currently scattered and poorly accessible to individual researchers. Based on a multistage Delphi process conducted by a multidisciplinary expert consortium as well as extensive community feedback, the present work provides a reliable and comprehensive common point of access to information on pitfalls related to validation metrics in image analysis. Although focused on biomedical image analysis, the addressed pitfalls generalize across application domains and are categorized according to a newly created, domain-agnostic taxonomy. The work serves to enhance global comprehension of a key topic in image analysis validation.

Published
2024

14. Multiplex Microscopy Assay for Assessment of Therapeutic and Serum Antibodies against Emerging Pathogens.

Author

Sartingen, Nuno, Stürmer, Vanessa, Kaltenböck, Matthias, Müller, Thorsten G., Schnitzler, Paul, Kreshuk, Anna, Kräusslich, Hans-Georg, Merle, Uta, Mücksch, Frauke, Müller, Barbara, Pape, Constantin, and Laketa, Vibor

Subjects
SARS-CoV-2, VIRAL antigens, PANDEMIC preparedness, FLUORESCENT proteins, BLOOD proteins
Abstract

The emergence of novel pathogens, exemplified recently by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need for rapidly deployable and adaptable diagnostic assays to assess their impact on human health and guide public health responses in future pandemics. In this study, we developed an automated multiplex microscopy assay coupled with machine learning-based analysis for antibody detection. To achieve multiplexing and simultaneous detection of multiple viral antigens, we devised a barcoding strategy utilizing a panel of HeLa-based cell lines. Each cell line expressed a distinct viral antigen, along with a fluorescent protein exhibiting a unique subcellular localization pattern for cell classification. Our robust, cell segmentation and classification algorithm, combined with automated image acquisition, ensured compatibility with a high-throughput approach. As a proof of concept, we successfully applied this approach for quantitation of immunoreactivity against different variants of SARS-CoV-2 spike and nucleocapsid proteins in sera of patients or vaccinees, as well as for the study of selective reactivity of monoclonal antibodies. Importantly, our system can be rapidly adapted to accommodate other SARS-CoV-2 variants as well as any antigen of a newly emerging pathogen, thereby representing an important resource in the context of pandemic preparedness. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
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15. A deep learning-based toolkit for 3D nuclei segmentation and quantitative analysis in cellular and tissue context.

Author

Vijayan, Athul, Mody, Tejasvinee Atul, Qin Yu, Wolny, Adrian, Cerrone, Lorenzo, Strauss, Soeren, Tsiantis, Miltos, Smith, Richard S., Hamprecht, Fred A., Kreshuk, Anna, and Schneitz, Kay

Subjects
PLANT cells & tissues, CELL analysis, NUCLEAR models, CELL nuclei, SOFTWARE visualization
Abstract

We present a new set of computational tools that enable accurate and widely applicable 3D segmentation of nuclei in various 3D digital organs. We have developed an approach for ground truth generation and iterative training of 3D nuclear segmentation models, which we applied to popular CellPose, PlantSeg and StarDist algorithms. We provide two high-quality models trained on plant nuclei that enable 3D segmentation of nuclei in datasets obtained from fixed or live samples, acquired from different plant and animal tissues, and stained with various nuclear stains or fluorescent protein-based nuclear reporters. We also share a diverse high-quality training dataset of about 10,000 nuclei. Furthermore, we advanced the MorphoGraphX analysis and visualization software by, among other things, providing a method for linking 3D segmented nuclei to their surrounding cells in 3D digital organs. We found that the nuclear-tocell volume ratio varies between different ovule tissues and during the development of a tissue. Finally, we extended the PlantSeg 3D segmentation pipeline with a proofreading tool that uses 3D segmented nuclei as seeds to correct cell segmentation errors in difficult-to-segment tissues. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
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18. Deep intravital brain tumor imaging enabled by tailored three-photon microscopy and analysis

Author

Marc Cicero Schubert, Stella Judith Soyka, Amr Tamimi, Emanuel Maus, Julian Schroers, Niklas Wißmann, Ekin Reyhan, Svenja Kristin Tetzlaff, Yvonne Yang, Robert Denninger, Robin Peretzke, Carlo Beretta, Michael Drumm, Alina Heuer, Verena Buchert, Alicia Steffens, Jordain Walshon, Kathleen McCortney, Sabine Heiland, Martin Bendszus, Peter Neher, Anna Golebiewska, Wolfgang Wick, Frank Winkler, Michael O. Breckwoldt, Anna Kreshuk, Thomas Kuner, Craig Horbinski, Felix Tobias Kurz, Robert Prevedel, and Varun Venkataramani

Subjects
Science
Abstract

Abstract Intravital 2P-microscopy enables the longitudinal study of brain tumor biology in superficial mouse cortex layers. Intravital microscopy of the white matter, an important route of glioblastoma invasion and recurrence, has not been feasible, due to low signal-to-noise ratios and insufficient spatiotemporal resolution. Here, we present an intravital microscopy and artificial intelligence-based analysis workflow (Deep3P) that enables longitudinal deep imaging of glioblastoma up to a depth of 1.2 mm. We find that perivascular invasion is the preferred invasion route into the corpus callosum and uncover two vascular mechanisms of glioblastoma migration in the white matter. Furthermore, we observe morphological changes after white matter infiltration, a potential basis of an imaging biomarker during early glioblastoma colonization. Taken together, Deep3P allows for a non-invasive intravital investigation of brain tumor biology and its tumor microenvironment at subcortical depths explored, opening up opportunities for studying the neuroscience of brain tumors and other model systems.

Published
2024
Full Text
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19. Multiplex Microscopy Assay for Assessment of Therapeutic and Serum Antibodies against Emerging Pathogens

Author

Nuno Sartingen, Vanessa Stürmer, Matthias Kaltenböck, Thorsten G. Müller, Paul Schnitzler, Anna Kreshuk, Hans-Georg Kräusslich, Uta Merle, Frauke Mücksch, Barbara Müller, Constantin Pape, and Vibor Laketa

Subjects
multiplex microscopy, machine learning, serology, emerging pathogens, monoclonal antibodies, SARS-CoV-2, Microbiology, QR1-502
Abstract

The emergence of novel pathogens, exemplified recently by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need for rapidly deployable and adaptable diagnostic assays to assess their impact on human health and guide public health responses in future pandemics. In this study, we developed an automated multiplex microscopy assay coupled with machine learning-based analysis for antibody detection. To achieve multiplexing and simultaneous detection of multiple viral antigens, we devised a barcoding strategy utilizing a panel of HeLa-based cell lines. Each cell line expressed a distinct viral antigen, along with a fluorescent protein exhibiting a unique subcellular localization pattern for cell classification. Our robust, cell segmentation and classification algorithm, combined with automated image acquisition, ensured compatibility with a high-throughput approach. As a proof of concept, we successfully applied this approach for quantitation of immunoreactivity against different variants of SARS-CoV-2 spike and nucleocapsid proteins in sera of patients or vaccinees, as well as for the study of selective reactivity of monoclonal antibodies. Importantly, our system can be rapidly adapted to accommodate other SARS-CoV-2 variants as well as any antigen of a newly emerging pathogen, thereby representing an important resource in the context of pandemic preparedness.

Published
2024
Full Text
View/download PDF

20. How to Build the Virtual Cell with Artificial Intelligence: Priorities and Opportunities.

Author

Bunne C, Roohani Y, Rosen Y, Gupta A, Zhang X, Roed M, Alexandrov T, AlQuraishi M, Brennan P, Burkhardt DB, Califano A, Cool J, Dernburg AF, Ewing K, Fox EB, Haury M, Herr AE, Horvitz E, Hsu PD, Jain V, Johnson GR, Kalil T, Kelley DR, Kelley SO, Kreshuk A, Mitchison T, Otte S, Shendure J, Sofroniew NJ, Theis F, Theodoris CV, Upadhyayula S, Valer M, Wang B, Xing E, Yeung-Levy S, Zitnik M, Karaletsos T, Regev A, Lundberg E, Leskovec J, and Quake SR

Abstract

The cell is arguably the most fundamental unit of life and is central to understanding biology. Accurate modeling of cells is important for this understanding as well as for determining the root causes of disease. Recent advances in artificial intelligence (AI), combined with the ability to generate large-scale experimental data, present novel opportunities to model cells. Here we propose a vision of leveraging advances in AI to construct virtual cells, high-fidelity simulations of cells and cellular systems under different conditions that are directly learned from biological data across measurements and scales. We discuss desired capabilities of such AI Virtual Cells, including generating universal representations of biological entities across scales, and facilitating interpretable in silico experiments to predict and understand their behavior using Virtual Instruments. We further address the challenges, opportunities and requirements to realize this vision including data needs, evaluation strategies, and community standards and engagement to ensure biological accuracy and broad utility. We envision a future where AI Virtual Cells help identify new drug targets, predict cellular responses to perturbations, as well as scale hypothesis exploration. With open science collaborations across the biomedical ecosystem that includes academia, philanthropy, and the biopharma and AI industries, a comprehensive predictive understanding of cell mechanisms and interactions has come into reach., Competing Interests: Competing interests C.B. and A. R. are employees of Genentech, a member of the Roche Group. A.R. has equity in Roche. A.R. was a co-founder and equity holder of Celsius Therapeutics, and is an equity holder in Immunitas. Until July 31, 2020 A.R. was an S.A.B. member of ThermoFisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics and Asimov. A.R. is a named inventor on multiple filed patents related to single cell and spatial genomics, including for scRNA-seq, spatial transcriptomics, Perturb-Seq, compressed experiments, and PerturbView. E.L. is an advisor for the Chan-Zuckerberg Initiative Foundation. N.J.S. is an employee of EvolutionaryScale, PBC.

Published
2024

21. Understanding metric-related pitfalls in image analysis validation.

Author

Reinke A, Tizabi MD, Baumgartner M, Eisenmann M, Heckmann-Nötzel D, Kavur AE, Rädsch T, Sudre CH, Acion L, Antonelli M, Arbel T, Bakas S, Benis A, Blaschko M, Buettner F, Cardoso MJ, Cheplygina V, Chen J, Christodoulou E, Cimini BA, Collins GS, Farahani K, Ferrer L, Galdran A, van Ginneken B, Glocker B, Godau P, Haase R, Hashimoto DA, Hoffman MM, Huisman M, Isensee F, Jannin P, Kahn CE, Kainmueller D, Kainz B, Karargyris A, Karthikesalingam A, Kenngott H, Kleesiek J, Kofler F, Kooi T, Kopp-Schneider A, Kozubek M, Kreshuk A, Kurc T, Landman BA, Litjens G, Madani A, Maier-Hein K, Martel AL, Mattson P, Meijering E, Menze B, Moons KGM, Müller H, Nichyporuk B, Nickel F, Petersen J, Rafelski SM, Rajpoot N, Reyes M, Riegler MA, Rieke N, Saez-Rodriguez J, Sánchez CI, Shetty S, van Smeden M, Summers RM, Taha AA, Tiulpin A, Tsaftaris SA, Calster BV, Varoquaux G, Wiesenfarth M, Yaniv ZR, Jäger PF, and Maier-Hein L

Abstract

Validation metrics are key for the reliable tracking of scientific progress and for bridging the current chasm between artificial intelligence (AI) research and its translation into practice. However, increasing evidence shows that particularly in image analysis, metrics are often chosen inadequately in relation to the underlying research problem. This could be attributed to a lack of accessibility of metric-related knowledge: While taking into account the individual strengths, weaknesses, and limitations of validation metrics is a critical prerequisite to making educated choices, the relevant knowledge is currently scattered and poorly accessible to individual researchers. Based on a multi-stage Delphi process conducted by a multidisciplinary expert consortium as well as extensive community feedback, the present work provides the first reliable and comprehensive common point of access to information on pitfalls related to validation metrics in image analysis. Focusing on biomedical image analysis but with the potential of transfer to other fields, the addressed pitfalls generalize across application domains and are categorized according to a newly created, domain-agnostic taxonomy. To facilitate comprehension, illustrations and specific examples accompany each pitfall. As a structured body of information accessible to researchers of all levels of expertise, this work enhances global comprehension of a key topic in image analysis validation.

Published
2024

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