Understanding Subsystems in Biology through Dimensionality Reduction, Graph Partitioning and Analytical Modeling

Biological systems exhibit rich and complex behavior through the orchestrated interplay of a large array of components. It is hypothesized that separable subsystems with some degree of functional autonomy exist; deciphering their independent behavior and functionality would greatly facilitate understanding the system as a whole. Discovering and analyzing such subsystems are hence pivotal problems in the quest to gain a quantitative understanding of complex biological systems. In this work, using approaches from machine learning, physics and graph theory, methods for the identification and analysis of such subsystems were developed. A novel methodology, based on a recent machine learning algorithm known as non-negative matrix factorization (NMF), was developed to discover such subsystems in a set of large-scale gene expression data. This set of subsystems was then used to predict functional relationships between genes, and this approach was shown to score significantly higher than conventional methods when benchmarking them against existing databases. Moreover, a mathematical treatment was developed to treat simple network subsystems based only on their topology (independent of particular parameter values). Application to a problem of experimental interest demonstrated the need for extentions to the conventional model to fully explain the experimental data. Finally, the notion of a subsystem was evaluated from a topological perspective. A number of different protein networks were examined to analyze their topological properties with respect to separability, seeking to find separable subsystems. These networks were shown to exhibit separability in a nonintuitive fashion, while the separable subsystems were of strong biological significance. It was demonstrated that the separability property found was not due to incomplete or biased data, but is likely to reflect biological structure.

Priors Stabilizers and Basis Functions: From Regularization to Radial, Tensor and Additive Splines

We had previously shown that regularization principles lead to approximation schemes, as Radial Basis Functions, which are equivalent to networks with one layer of hidden units, called Regularization Networks. In this paper we show that regularization networks encompass a much broader range of approximation schemes, including many of the popular general additive models, Breiman's hinge functions and some forms of Projection Pursuit Regression. In the probabilistic interpretation of regularization, the different classes of basis functions correspond to different classes of prior probabilities on the approximating function spaces, and therefore to different types of smoothness assumptions. In the final part of the paper, we also show a relation between activation functions of the Gaussian and sigmoidal type.

Hilbert space on probability density functions with Aitchison geometry

Compositional data analysis motivated the introduction of a complete Euclidean structure in the simplex of D parts. This was based on the early work of J. Aitchison (1986) and completed recently when Aitchinson distance in the simplex was associated with an inner product and orthonormal bases were identified (Aitchison and others, 2002; Egozcue and others, 2003). A partition of the support of a random variable generates a composition by assigning the probability of each interval to a part of the composition. One can imagine that the partition can be refined and the probability density would represent a kind of continuous composition of probabilities in a simplex of infinitely many parts. This intuitive idea would lead to a Hilbert-space of probability densities by generalizing the Aitchison geometry for compositions in the simplex into the set probability densities

Comparing methods for dimensionality reduction when data are density functions

Functional Data Analysis (FDA) deals with samples where a whole function is observed for each individual. A particular case of FDA is when the observed functions are density functions, that are also an example of infinite dimensional compositional data. In this work we compare several methods for dimensionality reduction for this particular type of data: functional principal components analysis (PCA) with or without a previous data transformation and multidimensional scaling (MDS) for diferent inter-densities distances, one of them taking into account the compositional nature of density functions. The difeerent methods are applied to both artificial and real data (households income distributions)

Web Graph

Slides and an essay on the Web Graph, search engines and how Google calculates Page Rank

Special Functions

Exam questions and solutions in LaTex

Special Functions pdf

Exam questions and solutions in PDF

MA167exam01pdf

Exam questions and solutions in PDF

MA160exam00

Exam questions and solutions in LaTex. Diagrams for the questions are all together in the support.zip file, as .eps files

MA160exam01

Exam questions and solutions in LaTex. Diagrams for the questions are all together in the support.zip file, as .eps files

MA160exam01pdf

Exam questions and solutions in PDF

MA160exam00pdf

Exam questions and solutions in PDF

MA167exam01

Exam questions and solutions in LaTex. Diagrams for the questions are all together in the support.zip file, as .eps files

Vector functions and curves

Exercises and solutions about vector functions and curves.