Closing the multichannel gap through computational reconstruction of interaction in super-resolution microscopy

Summary: Cellular function is defined by pathways that, in turn, are determined by distance-mediated interactions between and within subcellular organelles, protein complexes, and macromolecular structures. Multichannel super-resolution microscopy (SRM) is uniquely placed to quantify distance-mediat...

Full description

Saved in:
Bibliographic Details
Main Authors: Ben Cardoen, Hanene Ben Yedder, Ivan Robert Nabi, Ghassan Hamarneh
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Patterns
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666389925000297
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849312910719844352
author Ben Cardoen
Hanene Ben Yedder
Ivan Robert Nabi
Ghassan Hamarneh
author_facet Ben Cardoen
Hanene Ben Yedder
Ivan Robert Nabi
Ghassan Hamarneh
author_sort Ben Cardoen
collection DOAJ
description Summary: Cellular function is defined by pathways that, in turn, are determined by distance-mediated interactions between and within subcellular organelles, protein complexes, and macromolecular structures. Multichannel super-resolution microscopy (SRM) is uniquely placed to quantify distance-mediated interactions at the nanometer scale with its ability to label individual biological targets with independent markers that fluoresce in different spectra. We review novel computational methods that quantify interaction from multichannel SRM data in both point-cloud and voxel form. We discuss in detail SRM-specific factors that can compromise interaction analysis and decompose different classes of interactions based on distinct representative cell biology use cases, the underappreciated non-linear physics of their scale, and the development of specialized methods for those use cases. An abstract mathematical model is introduced to facilitate the comparison and evaluation of interaction reconstruction methods and to quantify the computational bottlenecks. We discuss the different strategies for validation of interaction analysis results with sparse or incomplete ground-truth data. Finally, evolving trends and future directions are presented, highlighting the “multichannel gap,” where interaction analysis is trailing behind the rapid increase in novel modes of multichannel SRM acquisitions. The bigger picture: Discovering how, where, and when interactions between proteins and organelles work is critical to unravel the molecular and cellular basis of cancer, metabolic, and degenerative diseases and how drugs can intervene. Super-resolution microscopy (SRM) is uniquely positioned to discover these interactions. We review novel interaction-analysis algorithms, and we identify specific SRM factors that can compromise the accuracy of interaction analysis. To evaluate these and future approaches, we introduce a mathematical framework, simplifying evaluation of existing and future algorithms. We highlight the “multichannel gap,” where interaction analysis finds itself lagging behind the rapid innovations in novel multichannel SRM microscopes, and review validation strategies. We offer cell biologists a gateway to quickly identify which method is needed to accurately discover complex interactions in the cell, opening new avenues for more precise drug discovery.
format Article
id doaj-art-ac0d9b2c62e744e7af48ea19d6f03618
institution Kabale University
issn 2666-3899
language English
publishDate 2025-05-01
publisher Elsevier
record_format Article
series Patterns
spelling doaj-art-ac0d9b2c62e744e7af48ea19d6f036182025-08-20T03:52:56ZengElsevierPatterns2666-38992025-05-016510118110.1016/j.patter.2025.101181Closing the multichannel gap through computational reconstruction of interaction in super-resolution microscopyBen Cardoen0Hanene Ben Yedder1Ivan Robert Nabi2Ghassan Hamarneh3Simon Fraser University, School of Computing Science, 8888 University Drive, Burnaby, BC V5A 1S6, Canada; University of British Columbia, Department of Cellular & Physiological Sciences, Faculty of Medicine, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Corresponding authorSimon Fraser University, School of Computing Science, 8888 University Drive, Burnaby, BC V5A 1S6, CanadaUniversity of British Columbia, Department of Cellular & Physiological Sciences, Faculty of Medicine, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; University of British Columbia, School of Biomedical Engineering, 2222 Health Sciences Mall, Vancouver, BC V6T1Z3, CanadaSimon Fraser University, School of Computing Science, 8888 University Drive, Burnaby, BC V5A 1S6, CanadaSummary: Cellular function is defined by pathways that, in turn, are determined by distance-mediated interactions between and within subcellular organelles, protein complexes, and macromolecular structures. Multichannel super-resolution microscopy (SRM) is uniquely placed to quantify distance-mediated interactions at the nanometer scale with its ability to label individual biological targets with independent markers that fluoresce in different spectra. We review novel computational methods that quantify interaction from multichannel SRM data in both point-cloud and voxel form. We discuss in detail SRM-specific factors that can compromise interaction analysis and decompose different classes of interactions based on distinct representative cell biology use cases, the underappreciated non-linear physics of their scale, and the development of specialized methods for those use cases. An abstract mathematical model is introduced to facilitate the comparison and evaluation of interaction reconstruction methods and to quantify the computational bottlenecks. We discuss the different strategies for validation of interaction analysis results with sparse or incomplete ground-truth data. Finally, evolving trends and future directions are presented, highlighting the “multichannel gap,” where interaction analysis is trailing behind the rapid increase in novel modes of multichannel SRM acquisitions. The bigger picture: Discovering how, where, and when interactions between proteins and organelles work is critical to unravel the molecular and cellular basis of cancer, metabolic, and degenerative diseases and how drugs can intervene. Super-resolution microscopy (SRM) is uniquely positioned to discover these interactions. We review novel interaction-analysis algorithms, and we identify specific SRM factors that can compromise the accuracy of interaction analysis. To evaluate these and future approaches, we introduce a mathematical framework, simplifying evaluation of existing and future algorithms. We highlight the “multichannel gap,” where interaction analysis finds itself lagging behind the rapid innovations in novel multichannel SRM microscopes, and review validation strategies. We offer cell biologists a gateway to quickly identify which method is needed to accurately discover complex interactions in the cell, opening new avenues for more precise drug discovery.http://www.sciencedirect.com/science/article/pii/S2666389925000297super-resolution microscopymultichannelcolocalizationinteractionsubcellular organelleprotein
spellingShingle Ben Cardoen
Hanene Ben Yedder
Ivan Robert Nabi
Ghassan Hamarneh
Closing the multichannel gap through computational reconstruction of interaction in super-resolution microscopy
Patterns
super-resolution microscopy
multichannel
colocalization
interaction
subcellular organelle
protein
title Closing the multichannel gap through computational reconstruction of interaction in super-resolution microscopy
title_full Closing the multichannel gap through computational reconstruction of interaction in super-resolution microscopy
title_fullStr Closing the multichannel gap through computational reconstruction of interaction in super-resolution microscopy
title_full_unstemmed Closing the multichannel gap through computational reconstruction of interaction in super-resolution microscopy
title_short Closing the multichannel gap through computational reconstruction of interaction in super-resolution microscopy
title_sort closing the multichannel gap through computational reconstruction of interaction in super resolution microscopy
topic super-resolution microscopy
multichannel
colocalization
interaction
subcellular organelle
protein
url http://www.sciencedirect.com/science/article/pii/S2666389925000297
work_keys_str_mv AT bencardoen closingthemultichannelgapthroughcomputationalreconstructionofinteractioninsuperresolutionmicroscopy
AT hanenebenyedder closingthemultichannelgapthroughcomputationalreconstructionofinteractioninsuperresolutionmicroscopy
AT ivanrobertnabi closingthemultichannelgapthroughcomputationalreconstructionofinteractioninsuperresolutionmicroscopy
AT ghassanhamarneh closingthemultichannelgapthroughcomputationalreconstructionofinteractioninsuperresolutionmicroscopy