naren ramakrishnan and richard f. helm departments of computer science and biochemistry virginia...
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From multivariate time course data, reconstruct (i) stages, (ii) transitions between stages, and (iii) properties that hold in each stageTRANSCRIPT
![Page 1: Naren Ramakrishnan and Richard F. Helm Departments of Computer Science and Biochemistry Virginia Tech, Blacksburg, VA 24061](https://reader036.vdocuments.site/reader036/viewer/2022062401/5a4d1afa7f8b9ab0599836ba/html5/thumbnails/1.jpg)
Naren Ramakrishnan and Richard F. HelmDepartments of Computer Science and BiochemistryVirginia Tech, Blacksburg, VA 24061
![Page 2: Naren Ramakrishnan and Richard F. Helm Departments of Computer Science and Biochemistry Virginia Tech, Blacksburg, VA 24061](https://reader036.vdocuments.site/reader036/viewer/2022062401/5a4d1afa7f8b9ab0599836ba/html5/thumbnails/2.jpg)
What we do How we do it Some discussion of biological results
Outline
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What we doFrom multivariate time course data, reconstruct (i) stages, (ii) transitions between stages, and (iii) properties that hold in each stage
![Page 4: Naren Ramakrishnan and Richard F. Helm Departments of Computer Science and Biochemistry Virginia Tech, Blacksburg, VA 24061](https://reader036.vdocuments.site/reader036/viewer/2022062401/5a4d1afa7f8b9ab0599836ba/html5/thumbnails/4.jpg)
What are temporal models?
Kripke structures
![Page 5: Naren Ramakrishnan and Richard F. Helm Departments of Computer Science and Biochemistry Virginia Tech, Blacksburg, VA 24061](https://reader036.vdocuments.site/reader036/viewer/2022062401/5a4d1afa7f8b9ab0599836ba/html5/thumbnails/5.jpg)
Temporal compartmentalization Yeast store carbohydrate and burn it in late G1
phase of the cell cycle: this superimposes a metabolic cycle over the cell cycle
Sequence of oxidative and reductive phases◦ O2 is used up to burn carbohydrates during oxidative phase◦ O2 levels increase and carbohydrate is stored in the
reductive phase Interplay between the YCC and YMC lead to
compartmentalization of biological processes in time◦ Cell cycle : reductive phase◦ Glycolysis and respiration occur at different times
![Page 6: Naren Ramakrishnan and Richard F. Helm Departments of Computer Science and Biochemistry Virginia Tech, Blacksburg, VA 24061](https://reader036.vdocuments.site/reader036/viewer/2022062401/5a4d1afa7f8b9ab0599836ba/html5/thumbnails/6.jpg)
Combined Kripke model
![Page 7: Naren Ramakrishnan and Richard F. Helm Departments of Computer Science and Biochemistry Virginia Tech, Blacksburg, VA 24061](https://reader036.vdocuments.site/reader036/viewer/2022062401/5a4d1afa7f8b9ab0599836ba/html5/thumbnails/7.jpg)
Segment the time course Identify biological processes enriched in
each segment Convert segmentation to a Kripke structure Merge Kripke structures into a dynamic
temporal model
How do we construct temporal models?
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Time series segmentation How do we identify “breakpoints” in the
time course? Intuition: A breakpoint is where there is
significant reorganization of clusters around segment boundaries.
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Modeling Cluster DynamicsA Cluster Dynamics Approach3602 genes, 3 clusters
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Modeling Cluster DynamicsA Cluster Dynamics Approach3602 genes, 3 clusters
Algorithm optimizes for this!
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A second example (YCC)
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Gantt charts of YMC
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Gantt chart of HP treatment
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Gantt chart of MD treatmentGantt chart of MD treatment
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![Page 16: Naren Ramakrishnan and Richard F. Helm Departments of Computer Science and Biochemistry Virginia Tech, Blacksburg, VA 24061](https://reader036.vdocuments.site/reader036/viewer/2022062401/5a4d1afa7f8b9ab0599836ba/html5/thumbnails/16.jpg)
Combined Kripke model again
![Page 17: Naren Ramakrishnan and Richard F. Helm Departments of Computer Science and Biochemistry Virginia Tech, Blacksburg, VA 24061](https://reader036.vdocuments.site/reader036/viewer/2022062401/5a4d1afa7f8b9ab0599836ba/html5/thumbnails/17.jpg)
Thank you