Modelling acute myeloid leukaemia in a continuum of differentiation states
Here we present a mathematical model of movement in an abstract space representing states of cellular differentiation. We motivate this work with recent examples that demonstrate a continuum of cellular differentiation using single-cell RNA-sequencing data to characterize cellular states in a high-d...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Intercollegiate Biomathematics Alliance
2018-06-01
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| Series: | Letters in Biomathematics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/23737867.2018.1472532 |
| _version_ | 1818324577425555456 |
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| author | H. Cho K. Ayers L. de Pills Y.-H. Kuo J. Park A. Radunskaya R. C. Rockne |
| author_facet | H. Cho K. Ayers L. de Pills Y.-H. Kuo J. Park A. Radunskaya R. C. Rockne |
| author_sort | H. Cho |
| collection | DOAJ |
| description | Here we present a mathematical model of movement in an abstract space representing states of cellular differentiation. We motivate this work with recent examples that demonstrate a continuum of cellular differentiation using single-cell RNA-sequencing data to characterize cellular states in a high-dimensional space, which is then mapped into $ \mathbb {R}^2 $ or $ \mathbb {R}^3 $ with dimension reduction techniques. We represent trajectories in the differentiation space as a graph, and model directed and random movement on the graph with partial differential equations. We hypothesize that flow in this space can be used to model normal and abnormal differentiation processes. We present a mathematical model of haematopoiesis parameterized with publicly available single-cell RNA-Seq data and use it to simulate the pathogenesis of acute myeloid leukaemia (AML). The model predicts the emergence of cells in novel intermediate states of differentiation consistent with immunophenotypic characterizations of a mouse model of AML. |
| first_indexed | 2024-12-13T11:30:48Z |
| format | Article |
| id | doaj.art-88632e367cd749d8b3a1a31047073e78 |
| institution | Directory Open Access Journal |
| issn | 2373-7867 |
| language | English |
| last_indexed | 2024-12-13T11:30:48Z |
| publishDate | 2018-06-01 |
| publisher | Intercollegiate Biomathematics Alliance |
| record_format | Article |
| series | Letters in Biomathematics |
| spelling | doaj.art-88632e367cd749d8b3a1a31047073e782022-12-21T23:47:57ZengIntercollegiate Biomathematics AllianceLetters in Biomathematics2373-78672018-06-0150S69S9810.1080/23737867.2018.14725321472532Modelling acute myeloid leukaemia in a continuum of differentiation statesH. Cho0K. Ayers1L. de Pills2Y.-H. Kuo3J. Park4A. Radunskaya5R. C. Rockne6University of MarylandPomona CollegeHarvey Mudd CollegeGehr Family Center for Leukemia Research, City of HopeHarvey Mudd CollegePomona CollegeDivision of Mathematical Oncology, City of HopeHere we present a mathematical model of movement in an abstract space representing states of cellular differentiation. We motivate this work with recent examples that demonstrate a continuum of cellular differentiation using single-cell RNA-sequencing data to characterize cellular states in a high-dimensional space, which is then mapped into $ \mathbb {R}^2 $ or $ \mathbb {R}^3 $ with dimension reduction techniques. We represent trajectories in the differentiation space as a graph, and model directed and random movement on the graph with partial differential equations. We hypothesize that flow in this space can be used to model normal and abnormal differentiation processes. We present a mathematical model of haematopoiesis parameterized with publicly available single-cell RNA-Seq data and use it to simulate the pathogenesis of acute myeloid leukaemia (AML). The model predicts the emergence of cells in novel intermediate states of differentiation consistent with immunophenotypic characterizations of a mouse model of AML.http://dx.doi.org/10.1080/23737867.2018.1472532Diffusion mappinghaematopoiesissingle-cell RNA-sequencingdevelopmental trajectoriesnonlinear dimension reductioncellular differentiationacute myeloid leukaemiadifferentiation continuum |
| spellingShingle | H. Cho K. Ayers L. de Pills Y.-H. Kuo J. Park A. Radunskaya R. C. Rockne Modelling acute myeloid leukaemia in a continuum of differentiation states Letters in Biomathematics Diffusion mapping haematopoiesis single-cell RNA-sequencing developmental trajectories nonlinear dimension reduction cellular differentiation acute myeloid leukaemia differentiation continuum |
| title | Modelling acute myeloid leukaemia in a continuum of differentiation states |
| title_full | Modelling acute myeloid leukaemia in a continuum of differentiation states |
| title_fullStr | Modelling acute myeloid leukaemia in a continuum of differentiation states |
| title_full_unstemmed | Modelling acute myeloid leukaemia in a continuum of differentiation states |
| title_short | Modelling acute myeloid leukaemia in a continuum of differentiation states |
| title_sort | modelling acute myeloid leukaemia in a continuum of differentiation states |
| topic | Diffusion mapping haematopoiesis single-cell RNA-sequencing developmental trajectories nonlinear dimension reduction cellular differentiation acute myeloid leukaemia differentiation continuum |
| url | http://dx.doi.org/10.1080/23737867.2018.1472532 |
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