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Linear Modeling of
Reduced-Order
Transcriptome Dynamics
Thomas Wood, Eli Shlizerman
● SVD/PCA of Transcriptome Time Series Data
● Optimal Discrete-Time Linear Dynamical System
● Optimal Continuous-Time Linear Dynamical
System
● Projection of Macroscale Interactions onto
Microscale
● Correlation between Inferred Interactions and
known Genetic Landscape
SVD/PCA of Transcriptome Time
Series Data
● We compared the effect of normalizing the features of the
transcriptome time series data before performing SVD
with doing singular value decomposition on a non-
normalized dataset.
● While this data has been subjected to analysis through
the SVD, no one has ever performed PCA on this
dataset.
Optimal Discrete-Time Linear
Dynamical System
● We followed the approach of D'hasseler et al. and found an
optimal state-space transition matrix to describe the reduced-
order dynamics of the transcriptome which were revealed
through the unsupervised learning step.
● Our approach was novel and differed from D'hasseler et al and
Wu et al in that we measured the performance of the transition
matrix with only one single matrix multiplication.
● The application of L1
regularized multivariate linear regression
to finding an optimal transition matrix is an original contribution
to the study of transcriptome modeling.
Optimal Continuous-Time Linear
Dynamical System
● We sought an optimal continous-time linear dynamical
system which could best describe the transcriptome
modes which were discovered through the unsupervised
learning step in our pipeline.
● Similar approaches (e.g. Inferrelator) that use
continuous-time linear dynamical systems model the
interactions of gene clusters and not the interactions of
non-correlating modes of transcriptome dynamics.
Projection of Macroscale
Interactions onto Microscale
● We were able to project the inferred relationships
between macroscale modes of the transcriptome onto the
microscale through finding a microscale transition matrix
according to the formula
⃗wk=∑
i
M
∑
j
M
ui
k
σi Ti
j
⃗uj/σ j
● This novel formula has never been applied before as
clustering is usually used to reduced the dimensionality of
the problem whereas our approach of using PCA/SVD
gives us the precise topology of each of our transcriptome
modes.
Correlation between Gene-Gene
Interactions and known Genetic
Landscape
● We calculated the Pearson Correlation Coefficient
between our matrix of genetic interactions and the
genetic lanscape of Costanzo et al (2010).
● We found the correlation between the interactions
inferred through our method and the gene-gene
associations of the genetic landscape to be
approximately zero.
● Our approach uses Singular Value Decomposition to
model collective behavior in the transcriptome on the
microscopic level.

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project_presentation

  • 1. Linear Modeling of Reduced-Order Transcriptome Dynamics Thomas Wood, Eli Shlizerman
  • 2. ● SVD/PCA of Transcriptome Time Series Data ● Optimal Discrete-Time Linear Dynamical System ● Optimal Continuous-Time Linear Dynamical System ● Projection of Macroscale Interactions onto Microscale ● Correlation between Inferred Interactions and known Genetic Landscape
  • 3.
  • 4. SVD/PCA of Transcriptome Time Series Data ● We compared the effect of normalizing the features of the transcriptome time series data before performing SVD with doing singular value decomposition on a non- normalized dataset. ● While this data has been subjected to analysis through the SVD, no one has ever performed PCA on this dataset.
  • 5.
  • 6.
  • 7.
  • 8. Optimal Discrete-Time Linear Dynamical System ● We followed the approach of D'hasseler et al. and found an optimal state-space transition matrix to describe the reduced- order dynamics of the transcriptome which were revealed through the unsupervised learning step. ● Our approach was novel and differed from D'hasseler et al and Wu et al in that we measured the performance of the transition matrix with only one single matrix multiplication. ● The application of L1 regularized multivariate linear regression to finding an optimal transition matrix is an original contribution to the study of transcriptome modeling.
  • 9. Optimal Continuous-Time Linear Dynamical System ● We sought an optimal continous-time linear dynamical system which could best describe the transcriptome modes which were discovered through the unsupervised learning step in our pipeline. ● Similar approaches (e.g. Inferrelator) that use continuous-time linear dynamical systems model the interactions of gene clusters and not the interactions of non-correlating modes of transcriptome dynamics.
  • 10.
  • 11.
  • 12. Projection of Macroscale Interactions onto Microscale ● We were able to project the inferred relationships between macroscale modes of the transcriptome onto the microscale through finding a microscale transition matrix according to the formula ⃗wk=∑ i M ∑ j M ui k σi Ti j ⃗uj/σ j ● This novel formula has never been applied before as clustering is usually used to reduced the dimensionality of the problem whereas our approach of using PCA/SVD gives us the precise topology of each of our transcriptome modes.
  • 13.
  • 14. Correlation between Gene-Gene Interactions and known Genetic Landscape ● We calculated the Pearson Correlation Coefficient between our matrix of genetic interactions and the genetic lanscape of Costanzo et al (2010). ● We found the correlation between the interactions inferred through our method and the gene-gene associations of the genetic landscape to be approximately zero. ● Our approach uses Singular Value Decomposition to model collective behavior in the transcriptome on the microscopic level.