Dataset Information

An image-based data-driven analysis of cellular architecture in a developing tissue.

ABSTRACT: Quantitative microscopy is becoming increasingly crucial in efforts to disentangle the complexity of organogenesis, yet adoption of the potent new toolbox provided by modern data science has been slow, primarily because it is often not directly applicable to developmental imaging data. We tackle this issue with a newly developed algorithm that uses point cloud-based morphometry to unpack the rich information encoded in 3D image data into a straightforward numerical representation. This enabled us to employ data science tools, including machine learning, to analyze and integrate cell morphology, intracellular organization, gene expression and annotated contextual knowledge. We apply these techniques to construct and explore a quantitative atlas of cellular architecture for the zebrafish posterior lateral line primordium, an experimentally tractable model of complex self-organized organogenesis. In doing so, we are able to retrieve both previously established and novel biologically relevant patterns, demonstrating the potential of our data-driven approach.

SUBMITTER: Hartmann J

PROVIDER: S-EPMC7274788 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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An image-based data-driven analysis of cellular architecture in a developing tissue.

Hartmann Jonas J Wong Mie M Gallo Elisa E Gilmour Darren D

eLife 20200605

Quantitative microscopy is becoming increasingly crucial in efforts to disentangle the complexity of organogenesis, yet adoption of the potent new toolbox provided by modern data science has been slow, primarily because it is often not directly applicable to developmental imaging data. We tackle this issue with a newly developed algorithm that uses point cloud-based morphometry to unpack the rich information encoded in 3D image data into a straightforward numerical representation. This enabled u ...[more]

PMID: 32501214

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Project description:ImportanceUndetected biological heterogeneity adversely impacts trials in Alzheimer's disease because rate of cognitive decline - and perhaps response to treatment - differs in subgroups. Recent results show that data-driven approaches can unravel the heterogeneity of Alzheimer's disease progression. The resulting stratification is yet to be leveraged in clinical trials.ObjectiveInvestigate whether image-based data-driven disease progression modelling could identify baseline biological heterogeneity in a clinical trial, and whether these subgroups have prognostic or predictive value.DesignScreening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study collected between April 2014 and December 2017, and longitudinal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) observational study downloaded in February 2022 were used.SettingThe A4 Study is an interventional trial involving 67 sites in the US, Canada, Australia, and Japan. ADNI is a multi-center observational study in North America.ParticipantsCognitively unimpaired amyloid-positive participants with a 3-Tesla T1-weighted MRI scan. Amyloid positivity was determined using florbetapir PET imaging (in A4) and CSF Aβ(1-42) (in ADNI).Main outcomes and measuresRegional volumes estimated from MRI scans were used as input to the Subtype and Stage Inference (SuStaIn) algorithm. Outcomes included cognitive test scores and SUVr values from florbetapir and flortaucipir PET.ResultsWe included 1,240 Aβ+ participants (and 407 Aβ- controls) from the A4 Study, and 731 A4-eligible ADNI participants. SuStaIn identified three neurodegeneration subtypes - Typical, Cortical, Subcortical - comprising 523 (42%) individuals. The remainder are designated subtype zero (insufficient atrophy). Baseline PACC scores (A4 primary outcome) were significantly worse in the Cortical subtype (median = -1.27, IQR=[-3.34,0.83]) relative to both subtype zero (median=-0.013, IQR=[-1.85,1.67], P<.0001) and the Subcortical subtype (median=0.03, IQR=[-1.78,1.61], P=.0006). In ADNI, over a four-year period (comparable to A4), greater cognitive decline in the mPACC was observed in both the Typical (-0.23/yr; 95% CI, [-0.41,-0.05]; P=.01) and Cortical (-0.24/yr; [-0.42,-0.06]; P=.009) subtypes, as well as the CDR-SB (Typical: +0.09/yr, [0.06,0.12], P<.0001; and Cortical: +0.07/yr, [0.04,0.10], P<.0001).Conclusions and relevanceIn a large secondary prevention trial, our image-based model detected neurodegenerative heterogeneity predictive of cognitive heterogeneity. We argue that such a model is a valuable tool to be considered in future trial design to control for previously undetected variance.

Project description:We aimed to assess the use of automatic machine learning (AutoML) algorithm based on magnetic resonance (MR) image data to assign prediction scores to patients with nasopharyngeal carcinoma (NPC). We also aimed to develop a 4-group classification system for NPC, superior to the current clinical staging system. Between January 2010 and January 2013, 792 patients with recent diagnosis of NPC, who had MR image data, were enrolled in the study. The AutoML algorithm was used and all statistical analyses were based on the 10-fold test. Primary endpoints included the probabilities of overall survival (OS), distant metastasis-free survival (DMFS), and local-region relapse-free survival (LRFS), and their sum was recorded as the final voting score, representative of progression-free survival (PFS) for each patient. The area under the receiver operating characteristic (ROC) curve generated from the MR image data-based model compared with the tumor, node, and metastasis (TNM) system-based model was 0.796 (P=0.008) for OS, 0.752 (P=0.053) for DMFS, and 0.721 (P=0.025) for LRFS. The Kaplan-Meier (KM) test values for II/I, III/II, IV/III groups in our new machine learning-based scoring system were 0.011, 0.010, and <0.001, respectively, whereas those for II/I, III/II, IV/III groups in the TNM/American Joint Committee on Cancer (AJCC) system were 0.118, 0.121, and <0.001, respectively. Significant differences were observed in the new machine learning-based scoring system analysis of each curve (P < 0.05), whereas the P values of curves obtained from the TNM/AJCC system, between II/I and III/II, were 0.118 and 0.121, respectively, without a significant difference. In conclusion, the AutoML algorithm demonstrated better prognostic performance than the TNM/AJCC system for NPC. The algorithm showed a good potential for clinical application and may aid in improving counseling and facilitate the personalized management of patients with NPC. The clinical application of our new scoring and staging system may significantly improve precision medicine.

Dataset Information

An image-based data-driven analysis of cellular architecture in a developing tissue.

Publications

An image-based data-driven analysis of cellular architecture in a developing tissue.

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