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@@ -0,0 +1,286 @@
+
+
+
+ 20240207T213731-503810327906f70a4bd187ed3df3dd546298e5d4
+ 20240207213731
+
+ JOSS Admin
+ admin@theoj.org
+
+ The Open Journal
+
+
+
+
+ Journal of Open Source Software
+ JOSS
+ 2475-9066
+
+ 10.21105/joss
+ https://joss.theoj.org
+
+
+
+
+ 02
+ 2024
+
+
+ 9
+
+ 94
+
+
+
+ HistoJS: Web-Based Analytical Tool for Advancing
+Multiplexed Images
+
+
+
+ Mohamed
+ Masoud
+ https://orcid.org/0000-0002-5365-242X
+
+
+ David
+ Gutman
+ https://orcid.org/0000-0002-1386-8701
+
+
+ Sergey
+ Plis
+ https://orcid.org/0000-0003-0040-0365
+
+
+
+ 02
+ 07
+ 2024
+
+
+ 6317
+
+
+ 10.21105/joss.06317
+
+
+ http://creativecommons.org/licenses/by/4.0/
+ http://creativecommons.org/licenses/by/4.0/
+ http://creativecommons.org/licenses/by/4.0/
+
+
+
+ Software archive
+ 10.5281/zenodo.10626533
+
+
+ GitHub review issue
+ https://github.com/openjournals/joss-reviews/issues/6317
+
+
+
+ 10.21105/joss.06317
+ https://joss.theoj.org/papers/10.21105/joss.06317
+
+
+ https://joss.theoj.org/papers/10.21105/joss.06317.pdf
+
+
+
+
+
+ The digital slide archive: A software
+platform for management, integration, and analysis of histology for
+cancer research
+ Gutman
+ Cancer research
+ 21
+ 77
+ 10.1158/0008-5472.CAN-17-0629
+ 2017
+ Gutman, D. A., Khalilia, M., Lee, S.,
+Nalisnik, M., Mullen, Z., Beezley, J., Chittajallu, D. R., Manthey, D.,
+& Cooper, L. A. (2017). The digital slide archive: A software
+platform for management, integration, and analysis of histology for
+cancer research. Cancer Research, 77(21), e75–e78.
+https://doi.org/10.1158/0008-5472.CAN-17-0629
+
+
+ OpenSeadragon
+ OpenSeadragon dev. team
+ 2022
+ OpenSeadragon dev. team. (2022).
+OpenSeadragon. GitHub Pages.
+http://openseadragon.github.io/
+
+
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+using a high-throughput cyclic immunofluorescence method
+ Lin
+ Nature communications
+ 1
+ 6
+ 10.1038/ncomms9390
+ 2015
+ Lin, J.-R., Fallahi-Sichani, M.,
+& Sorger, P. K. (2015). Highly multiplexed imaging of single cells
+using a high-throughput cyclic immunofluorescence method. Nature
+Communications, 6(1), 8390.
+https://doi.org/10.1038/ncomms9390
+
+
+ Highly multiplexed immunofluorescence imaging
+of human tissues and tumors using t-CyCIF and conventional optical
+microscopes
+ Lin
+ elife
+ 7
+ 10.7554/eLife.31657
+ 2018
+ Lin, J.-R., Izar, B., Wang, S., Yapp,
+C., Mei, S., Shah, P. M., Santagata, S., & Sorger, P. K. (2018).
+Highly multiplexed immunofluorescence imaging of human tissues and
+tumors using t-CyCIF and conventional optical microscopes. Elife, 7.
+https://doi.org/10.7554/eLife.31657
+
+
+ Highly multiplexed single-cell analysis of
+formalin-fixed, paraffin-embedded cancer tissue
+ Gerdes
+ Proceedings of the National Academy of
+Sciences
+ 29
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+ 10.1073/pnas.1300136110
+ 2013
+ Gerdes, M. J., Sevinsky, C. J., Sood,
+A., Adak, S., Bello, M. O., Bordwell, A., Can, A., Corwin, A., Dinn, S.,
+Filkins, R. J., & others. (2013). Highly multiplexed single-cell
+analysis of formalin-fixed, paraffin-embedded cancer tissue. Proceedings
+of the National Academy of Sciences, 110(29), 11982–11987.
+https://doi.org/10.1073/pnas.1300136110
+
+
+ Cell detection with star-convex
+polygons
+ Schmidt
+ Medical image computing and computer assisted
+intervention–MICCAI 2018: 21st international conference, granada, spain,
+september 16-20, 2018, proceedings, part II 11
+ 10.1007/978-3-030-00934-2_30
+ 2018
+ Schmidt, U., Weigert, M., Broaddus,
+C., & Myers, G. (2018). Cell detection with star-convex polygons.
+Medical Image Computing and Computer Assisted Intervention–MICCAI 2018:
+21st International Conference, Granada, Spain, September 16-20, 2018,
+Proceedings, Part II 11, 265–273.
+https://doi.org/10.1007/978-3-030-00934-2_30
+
+
+ A new statistical approach to geographic
+variation analysis
+ Gabriel
+ Systematic zoology
+ 3
+ 18
+ 10.2307/2412323
+ 1969
+ Gabriel, K. R., & Sokal, R. R.
+(1969). A new statistical approach to geographic variation analysis.
+Systematic Zoology, 18(3), 259–278.
+https://doi.org/10.2307/2412323
+
+
+ Deep profiling of mouse splenic architecture
+with CODEX multiplexed imaging
+ Goltsev
+ Cell
+ 4
+ 174
+ 10.1016/j.cell.2018.07.010
+ 2018
+ Goltsev, Y., Samusik, N.,
+Kennedy-Darling, J., Bhate, S., Hale, M., Vazquez, G., Black, S., &
+Nolan, G. P. (2018). Deep profiling of mouse splenic architecture with
+CODEX multiplexed imaging. Cell, 174(4), 968–981.
+https://doi.org/10.1016/j.cell.2018.07.010
+
+
+ Multiplexed ion beam imaging of human breast
+tumors
+ Angelo
+ Nature medicine
+ 4
+ 20
+ 10.1038/nm.3488
+ 2014
+ Angelo, M., Bendall, S. C., Finck,
+R., Hale, M. B., Hitzman, C., Borowsky, A. D., Levenson, R. M., Lowe, J.
+B., Liu, S. D., Zhao, S., & others. (2014). Multiplexed ion beam
+imaging of human breast tumors. Nature Medicine, 20(4), 436–442.
+https://doi.org/10.1038/nm.3488
+
+
+ QuPath: Open source software for digital
+pathology image analysis
+ Bankhead
+ Scientific reports
+ 1
+ 7
+ 10.1038/s41598-017-17204-5
+ 2017
+ Bankhead, P., Loughrey, M. B.,
+Fernández, J. A., Dombrowski, Y., McArt, D. G., Dunne, P. D., McQuaid,
+S., Gray, R. T., Murray, L. J., Coleman, H. G., & others. (2017).
+QuPath: Open source software for digital pathology image analysis.
+Scientific Reports, 7(1), 1–7.
+https://doi.org/10.1038/s41598-017-17204-5
+
+
+ TensorFlow.js: Machine learning for the web
+and beyond
+ Smilkov
+ arXiv
+ 10.48550/arXiv.1901.05350
+ 2019
+ Smilkov, D., Thorat, N., Assogba, Y.,
+Nicholson, C., Kreeger, N., Yu, P., Cai, S., Nielsen, E., Soegel, D.,
+& others. (2019). TensorFlow.js: Machine learning for the web and
+beyond. arXiv.
+https://doi.org/10.48550/arXiv.1901.05350
+
+
+ Lung dataset-1
+ Rashid
+ 10.7303/syn17865732
+ 2019
+ Rashid, R., & others. (2019).
+Lung dataset-1. Synapse repository.
+https://doi.org/10.7303/syn17865732
+
+
+ Beyond authorship: Attribution, contribution,
+collaboration, and credit
+ Brand
+ Learned Publishing
+ 2
+ 28
+ 10.1087/20150211
+ 2015
+ Brand, A., Allen, L., Altman, M.,
+Hlava, M., & Scott, J. (2015). Beyond authorship: Attribution,
+contribution, collaboration, and credit. Learned Publishing, 28(2),
+151–155. https://doi.org/10.1087/20150211
+
+
+
+
+
+
diff --git a/joss.06317/10.21105.joss.06317.jats b/joss.06317/10.21105.joss.06317.jats
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+++ b/joss.06317/10.21105.joss.06317.jats
@@ -0,0 +1,556 @@
+
+
+
+
+
+
+
+Journal of Open Source Software
+JOSS
+
+2475-9066
+
+Open Journals
+
+
+
+6317
+10.21105/joss.06317
+
+HistoJS: Web-Based Analytical Tool for Advancing
+Multiplexed Images
+
+
+
+https://orcid.org/0000-0002-5365-242X
+
+Masoud
+Mohamed
+
+
+*
+
+
+https://orcid.org/0000-0002-1386-8701
+
+Gutman
+David
+
+
+
+
+https://orcid.org/0000-0003-0040-0365
+
+Plis
+Sergey
+
+
+
+
+
+
+Tri-institutional Center for Translational Research in
+Neuroimaging and Data Science (TReNDS), Georgia State University,
+Georgia Institute of Technology, Emory University, Atlanta, United
+States of America
+
+
+
+
+Department of Computer Science, Georgia State University,
+Atlanta, United States of America
+
+
+
+
+Department of Pathology, Emory University School of
+Medicine, Atlanta, United States of America
+
+
+
+
+* E-mail:
+
+
+25
+12
+2023
+
+9
+94
+6317
+
+Authors of papers retain copyright and release the
+work under a Creative Commons Attribution 4.0 International License (CC
+BY 4.0)
+2022
+The article authors
+
+Authors of papers retain copyright and release the work under
+a Creative Commons Attribution 4.0 International License (CC BY
+4.0)
+
+
+
+Visualization
+Web Machine Learning
+Multiplexed Images
+Spatial Biology
+Single Cell
+
+
+
+
+
+ Summary
+
Advances in multiplexed imaging technologies enable us to capture
+ spatial single-cell proteomics and transcriptomics data in
+ unprecedented detail and with high spatial resolution. This large
+ volume of image data presents a challenge in accurately isolating and
+ quantifying distinct cell types to understand disease complexity,
+ neurological disorders, potential biomarkers, and targets for drug
+ development. Therefore, there is an incremental demand and challenges
+ to developing and validating cutting-edge quantitative image analysis
+ tools for diagnosis, prognosis, and therapy response prediction and
+ assessment in neurological and oncological diseases.
+ HistoJS
+ is a newly developed web-based tool that aims to overcome the
+ challenges of utilizing highly-multiplexed immunofluorescence (mIF)
+ images
+ (Lin
+ et al., 2015) for spatial biology research. It provides
+ open-source and extensible tool for analyzing spatial-molecular
+ patterns, enabling a deeper view of the single-cell spatial
+ relationship, along with machine learning algorithms in an easy-to-use
+ interactive interface for the biomedical community.
+
+
+ Statement of need
+
Single-cell data have the potential to enhance our understanding of
+ biological systems, shedding light on disease mechanisms and
+ reactions. The data from single-cell sequencing and multiplexed
+ imaging technologies have distinctive capabilities for cell
+ phenotyping, clustering, and landscape analysis. However, handling
+ large-scale multiplexed image datasets generated from advanced imaging
+ technologies and narrowing the lag between those technologies and the
+ existing analytical tools remains challenging. There is a need to
+ effectively utilize subcellular imaging data by storing, retrieving,
+ visualizing, and performing quantitative analysis of those big data.
+ Addressing the challenges posed by highly multiplexed image analysis,
+ HistoJS emerges as an open-source and adaptable tool for visualizing
+ and analyzing intricate biological processes with spatial subcellular
+ resolution. It offers a graphical user interface for effortless
+ navigation through stored multiplexed images, allowing dynamic
+ selection of image channels for composite views. HistoJS encompasses a
+ diverse set of image processing and machine learning algorithms to
+ support essential analysis, including real-time cell segmentation,
+ phenotyping, classification, correlations, spatial analysis, and
+ quantification of cell types to unveil interactions within the tissue
+ samples. These functionalities are provided in an easy-to-use
+ interactive interface to help biomedical users and related groups
+ understand the progression of neurological and oncological diseases
+ and find clinical outcomes. Other commercial tools like the VisioPharm
+ suite are expensive and complicated to be customized by the
+ informatics community to meet the specific needs of cancer
+ researchers. QuPath
+ (Bankhead
+ et al., 2017), another popular open-source tool, has some
+ useful features for the analysis that are not web-based and need more
+ key features for whole slide image analysis. Positioned as a web-based
+ solution, HistoJS focuses on enhancing usability, accessibility,
+ sustainability, scalability, and collaboration. Boosting user-friendly
+ interfaces and cross-platform compatibility, HistoJS ensures a
+ seamless and accessible experience. The sustainability of HistoJS is
+ realized through centralized updates and reduced hardware
+ dependencies, streamlining management and minimizing hardware
+ requirements.
+
+
+ Background
+
Advanced High-plex imaging technologies, such as Multiplexed
+ Immunofluorescence (MxIF)
+ (Gerdes
+ et al., 2013), tissue-based cyclic immunofluorescence (t-CyCIF)
+ (Lin
+ et al., 2018), CO-Detection by indEXing (CODEX)
+ (Goltsev
+ et al., 2018), and Multiplexed Ion Beam Imaging (MIBI)
+ (Angelo
+ et al., 2014), facilitate the study of intricate biological
+ processes with precise spatial subcellular resolution. While MIBI
+ utilizes a mass spectrometry-based approach, the other technologies
+ utilize conventional fluorescence microscopes, and all enable the
+ simultaneous detection of 50+ antigens within a single tissue section.
+ These technologies offer invaluable insights into the complexities of
+ biological systems. The process typically commences with sample
+ preparation of high-quality formaldehyde-fixed and paraffin-embedded
+ (FFPE) tissue sections (e.g., biopsy, surgical specimen) that can pass
+ through either an iterative, multicycle image acquisition pipeline as
+ CODEX or a non-iterative single imaging cycle, such as MIBI. Either
+ approach produces a stack of raw microscopy image tiles that need
+ stitching with drift correction and then registration across channels
+ to generate large-scale mosaic images in OME-TIFF (open microscopy
+ environment-tagged image file format). Each channel represents the
+ spectral signal from a specific marker or antigen in the tissue. Other
+ preprocessing steps include image deconvolution to minimize image
+ blurring, noise reduction to reduce background and autofluorescence
+ noise, and artifact removal that addresses image artifacts (e.g.,
+ axial and lateral tile drift). Preprocessing steps are essential to
+ enhance the quality of the raw data and prepare it for downstream
+ analysis. The goal is to identify, localize, and count different cell
+ types to study their population and interactions.
+
+
+ Pipeline
+
For hosting and organizing user data, the Digital Slide Archive
+ (DSA), an open-source platform, is used as a data hosting environment
+ (Gutman
+ et al., 2017). DSA is a reliable containerized web-based
+ platform that can store and manage large image datasets such as
+ immunofluorescence image data. DSA components include a MongoDB
+ database, a job execution/scheduler (girder worker), and a Secure data
+ management system (Girder) that provides RESTful APIs to allow
+ programmatic control over image data and metadata while providing user
+ access controls. DSA is easy to install locally on the user side or
+ remotely on the cloud. HistoJS uses DSA as a backend to manage user
+ images locally or remotely and store analysis results according to
+ end-user preferences. To visualize mIF images in HistoJS,
+ OpenSeadragon
+ (OpenSeadragon
+ dev. team, 2022), an open-source web-based viewer, is used.
+ HistoJS has rich JavaScript functions to support different types of
+ canvas rendering global Composite operations, giving the best insight
+ into data with panning, zooming, and overlay options. To that end, we
+ were able to make HistoJS suitable for building a customized stack of
+ protein channels and composite them in a high resolution and full
+ scale as illustrated in
+ [fig:HistoJS-Overview].
+ The analytical components of HistoJS include cell segmentation,
+ phenotyping, classification, correlations, spatial analysis, and
+ quantification of cell types to discover cell interactions. We tackled
+ the challenges in real time; fast and reliable techniques are used to
+ expedite the extraction of cell boundaries
+ (Schmidt
+ et al., 2018) and morphological features (e.g., solidity,
+ eccentricity, orientation, etc.). Cell neighbor detections are tackled
+ with spatial plotting and analysis by computing Delaunay neighborhood
+ graphs
+ (Gabriel
+ & Sokal, 1969).
+
+
HistoJS graphical interface overview. Biological
+ statistical tasks such as biological cell biomarkers histogram,
+ sample statistics quartiles, cell classification, correlations,
+ spatial analysis, and quantification of specific marker expression
+ are available for cell analysis and discovering the cell
+ interactions. (Dataset
+ (Rashid
+ & others,
+ 2019)).
+
+
+
Although the tool is suitable for cluster-based deployment, it can
+ also be deployed on the cloud or locally on the client side. With an
+ average GPU GeForce GTX 1050 Ti of 768 cores/ 4GB buffer, 7Gbps memory
+ speed, Intel® Core™ i7-8700 CPU @ 3.20GHz × 12, and a system memory of
+ 16 GB, HistoJS shows in general fast response while rendering and
+ processing immunofluorescence images, with the potential for better
+ performance thanks to the
+ TensorFlow.js(Smilkov
+ et al., 2019) Web Graphics Library ( WebGL-2) backbone.
+
+
+ Code availability
+
HistoJS source code is publicly accessible in the GitHub repository
+ (https://github.com/Mmasoud1/HistoJS).
+ Multiple DSA online servers can be accessed from HistoJS such as
+ https://styx.neurology.emory.edu/girder/
+ to load mIF data samples and test the tool performance. Researchers
+ could visualize and analyze the expression patterns of key biomarkers
+ associated with diseases and disorders. The platform’s interactive
+ features facilitated the identification of disease-specific
+ signatures, providing valuable insights into the molecular basis of
+ diseases.
+
Detailed step-by-step
+ documentation
+ is provided along with HistoJS
+ live
+ demo.
+
+
+ Author contributions
+
We describe contributions to this paper using the CRediT taxonomy
+ (Brand
+ et al., 2015). Writing – Original Draft: M.M.; Writing – Review
+ & Editing: M.M., and S.P.; Conceptualization and methodology:
+ M.M., and D.G.; Software and data curation: M.M.; Validation: M.M.,
+ and S.P.; Resources: D.G.; Visualization: M.M.; Project
+ Administration: M.M.
+
+
+
+
+
+
+
+ GutmanDavid A
+ KhaliliaMohammed
+ LeeSanghoon
+ NalisnikMichael
+ MullenZach
+ BeezleyJonathan
+ ChittajalluDeepak R
+ MantheyDavid
+ CooperLee AD
+
+ The digital slide archive: A software platform for management, integration, and analysis of histology for cancer research
+
+ AACR
+ 2017
+ 77
+ 21
+ 10.1158/0008-5472.CAN-17-0629
+ e75
+ e78
+
+
+
+
+
+ OpenSeadragon dev. team
+
+ OpenSeadragon
+ GitHub Pages
+ 2022
+ http://openseadragon.github.io/
+
+
+
+
+
+ LinJia-Ren
+ Fallahi-SichaniMohammad
+ SorgerPeter K
+
+ Highly multiplexed imaging of single cells using a high-throughput cyclic immunofluorescence method
+
+ Nature Publishing Group UK London
+ 2015
+ 6
+ 1
+ 10.1038/ncomms9390
+ 8390
+
+
+
+
+
+
+ LinJia-Ren
+ IzarBenjamin
+ WangShu
+ YappClarence
+ MeiShaolin
+ ShahParin M
+ SantagataSandro
+ SorgerPeter K
+
+ Highly multiplexed immunofluorescence imaging of human tissues and tumors using t-CyCIF and conventional optical microscopes
+
+ eLife Sciences Publications, Ltd
+ 2018
+ 7
+ 10.7554/eLife.31657
+
+
+
+
+
+ GerdesMichael J
+ SevinskyChristopher J
+ SoodAnup
+ AdakSudeshna
+ BelloMusodiq O
+ BordwellAlexander
+ CanAli
+ CorwinAlex
+ DinnSean
+ FilkinsRobert J
+ others
+
+ Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue
+
+ National Acad Sciences
+ 2013
+ 110
+ 29
+ 10.1073/pnas.1300136110
+ 11982
+ 11987
+
+
+
+
+
+ SchmidtUwe
+ WeigertMartin
+ BroaddusColeman
+ MyersGene
+
+ Cell detection with star-convex polygons
+
+ Springer
+ 2018
+ 10.1007/978-3-030-00934-2_30
+ 265
+ 273
+
+
+
+
+
+ GabrielK Ruben
+ SokalRobert R
+
+ A new statistical approach to geographic variation analysis
+
+ Society of Systematic Zoology
+ 1969
+ 18
+ 3
+ 10.2307/2412323
+ 259
+ 278
+
+
+
+
+
+ GoltsevYury
+ SamusikNikolay
+ Kennedy-DarlingJulia
+ BhateSalil
+ HaleMatthew
+ VazquezGustavo
+ BlackSarah
+ NolanGarry P
+
+ Deep profiling of mouse splenic architecture with CODEX multiplexed imaging
+
+ Elsevier
+ 2018
+ 174
+ 4
+ 10.1016/j.cell.2018.07.010
+ 968
+ 981
+
+
+
+
+
+ AngeloMichael
+ BendallSean C
+ FinckRachel
+ HaleMatthew B
+ HitzmanChuck
+ BorowskyAlexander D
+ LevensonRichard M
+ LoweJohn B
+ LiuScot D
+ ZhaoShuchun
+ others
+
+ Multiplexed ion beam imaging of human breast tumors
+
+ Nature Publishing Group US New York
+ 2014
+ 20
+ 4
+ 10.1038/nm.3488
+ 436
+ 442
+
+
+
+
+
+ BankheadPeter
+ LoughreyMaurice B
+ FernándezJosé A
+ DombrowskiYvonne
+ McArtDarragh G
+ DunnePhilip D
+ McQuaidStephen
+ GrayRonan T
+ MurrayLiam J
+ ColemanHelen G
+ others
+
+ QuPath: Open source software for digital pathology image analysis
+
+ Nature Publishing Group
+ 2017
+ 7
+ 1
+ 10.1038/s41598-017-17204-5
+ 1
+ 7
+
+
+
+
+
+ SmilkovD.
+ ThoratN.
+ AssogbaY.
+ NicholsonC.
+ KreegerN.
+ YuP.
+ CaiS.
+ NielsenE.
+ SoegelD.
+ others
+
+ TensorFlow.js: Machine learning for the web and beyond
+
+ 2019
+ 10.48550/arXiv.1901.05350
+
+
+
+
+
+ RashidR.
+ others
+
+ Lung dataset-1
+ Synapse repository
+ 2019
+ 10.7303/syn17865732
+
+
+
+
+
+ BrandAmy
+ AllenLiz
+ AltmanMicah
+ HlavaMarjorie
+ ScottJo
+
+ Beyond authorship: Attribution, contribution, collaboration, and credit
+
+ 2015
+ 28
+ 2
+ https://onlinelibrary.wiley.com/doi/abs/10.1087/20150211
+ 10.1087/20150211
+ 151
+ 155
+
+
+
+
+
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