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Record W4282931903 · doi:10.1158/1538-7445.am2022-2734

Abstract 2734: Integrating hybrid spatiotemporal models and multiscale data for the study of cancer progression in 3D cultures

2022· article· en· W4282931903 on OpenAlexaff
Nikolaos M. Dimitriou, Salvador Flores-Torres, Maria Kyriakidou, Joseph M. Kinsella, Georgios D. Mitsis

Bibliographic record

VenueCancer Research · 2022
Typearticle
Languageen
FieldMathematics
TopicMathematical Biology Tumor Growth
Canadian institutionsMcGill University
Fundersnot available
KeywordsCancerCancer cellMetastasisSpatial analysisChemotaxisBiologyComputational biologyBiological systemComputer scienceMathematicsGeneticsStatistics

Abstract

fetched live from OpenAlex

Abstract Tumour progression consists of various stages including migration to the surrounding tissues, leading to metastasis [1]. In this work, we investigate the multiscale quantitative characteristics of the spatial organization and migration of cancer in 3D cultures. For this study, we combined 3D cell culture experiments of Triple Negative Breast Cancer (TNBC) cells, hybrid spatiotemporal models, and longitudinal RNA-sequencing data analysis. The experiments included two experimental conditions; simple growth experiments, and experiments of growth in presence of the migrastatic drug Paclitaxel. The spatial distributions of the cells enabled us to calibrate and validate a hybrid Keller-Segel model, incorporated into a novel computational framework capable of interpreting the relation between morphological patterns and the underlying mechanisms of cancer growth [2]. The RNA-seq data included different time-points with and without treatment. The results suggested that cancer cells exhibited biased movement towards the bottom of the space, a movement that was inhibited in the presence of Paclitaxel. The calibrated model was able to describe the overall characteristics of the experimental observations, and suggested that cancer cells exhibited chemotactic migration and cell accumulation, as well as random motion throughout the period of development. The spatial pattern analysis revealed transient, non-random spatial distributions of cancer cells that consisted of clustered patterns across a wide range of neighbourhood distances, as well as dispersion for larger distances. The RNA-seq data exhibited coherence with the chemotactic migration hypothesis of the mathematical model, indicating significant under-representation of the Gene Ontology (GO) terms related to chemotactic migration in presence of the migrastatic drug. Overall, this study provided an insightful quantitative characterization of the spatiotemporal organization and progression of TNBC cells in 3D cultures. We anticipate that these developments will enable us to expand our studies to more realistic conditions, including the introduction of heterogeneic cell populations. References [1] Friedl, P., Locker, J., Sahai, E., & Segall, J. E. (2012). Classifying collective cancer cell invasion.Nature Cell Biology, 14(8), 777-783. [2] Dimitriou, N. M., Flores-Torres, S., Kinsella, J. M., & Mitsis, G. D. (2021). Validating hybrid spatiotemporal models of tumour growth with 3D cell culture data. 3rd International Symposium on Mathematical and Computational Oncology. Citation Format: Nikolaos Dimitriou, Salvador Flores-Torres, Maria Kyriakidou, Joseph Matthew Kinsella, Georgios Mitsis. Integrating hybrid spatiotemporal models and multiscale data for the study of cancer progression in 3D cultures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2734.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.574
Threshold uncertainty score0.375

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.329
GPT teacher head0.537
Teacher spread0.208 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2022
Admission routes1
Has abstractyes

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