Methods for inference and analysis of gene networks from RNA sequencing data

RNA (Ribonuceic Acid) sequencing technology is a powerful technology used to give re- searchers essential information about the functionality of genes. The transcriptomic study and downstream analysis highlight the functioning of the genes associated with a specific biological process/treatment. In practice, differentially expressed genes associated with a particular treatment or genotype are subjected to downstream analysis to find some critical set of genes. This critical set of genes/ genes pathways infers the effect of the treatment in a cell or tissue. This disserta- tion describes the multiple stages framework of finding these critical sets of genes using different analysis methodologies and inference algorithms. RNA sequencing technology helps to find the differentially expressed genes associated with the treatments and genotypes. The preliminary step of RNA-seq analysis consists of extracting the mRNA(messenger RNA) followed by mRNA libraries’ preparation and sequencing using the Illumina HiSeq 2000 platform. The later stage analysis starts with mapping the RNA sequencing data (obtained from the previous step) to the genome annotations and counting each annotated gene’s reads to produce the gene expression data. The second step involves using the statistical method such as linear model fit, clustering, and probabilistic graphical modeling to analyze genes and gene networks’ role in treatment responses. In this dissertation, an R software package is developed that compiles all the RNA sequencing steps and the downstream analysis using the R software and Linux environment. Inference methodology based on loopy belief propagation is conducted on the gene networks to infer the differential expression of the gene in the further step. The loopy belief propagation algorithm uses a computational modeling framework that takes the gene expression data and the transcriptional Factor interacting with the genes. The inference method starts with constructing a gene-Transcriptional Factor network. The construction of the network uses an undirected proba- bilistic graphical modeling approach. Later the belief message is propagated across all the nodes of the graphs. The analysis and inference methods explained in the dissertation were applied to the Arabidopsis plant with two different genotypes subjected to two different stress treatments. The results for the analysis and inference methods are reported in the dissertation

3D shape matching and registration : a probabilistic perspective

Dense correspondence is a key area in computer vision and medical image analysis. It has applications in registration and shape analysis. In this thesis, we develop a technique to recover dense correspondences between the surfaces of neuroanatomical objects over heterogeneous populations of individuals. We recover dense correspondences based on 3D shape matching. In this thesis, the 3D shape matching problem is formulated under the framework of Markov Random Fields (MRFs). We represent the surfaces of neuroanatomical objects as genus zero voxel-based meshes. The surface meshes are projected into a Markov random field space. The projection carries both geometric and topological information in terms of Gaussian curvature and mesh neighbourhood from the original space to the random field space. Gaussian curvature is projected to the nodes of the MRF, and the mesh neighbourhood structure is projected to the edges. 3D shape matching between two surface meshes is then performed by solving an energy function minimisation problem formulated with MRFs. The outcome of the 3D shape matching is dense point-to-point correspondences. However, the minimisation of the energy function is NP hard. In this thesis, we use belief propagation to perform the probabilistic inference for 3D shape matching. A sparse update loopy belief propagation algorithm adapted to the 3D shape matching is proposed to obtain an approximate global solution for the 3D shape matching problem. The sparse update loopy belief propagation algorithm demonstrates significant efficiency gain compared to standard belief propagation. The computational complexity and convergence property analysis for the sparse update loopy belief propagation algorithm are also conducted in the thesis. We also investigate randomised algorithms to minimise the energy function. In order to enhance the shape matching rate and increase the inlier support set, we propose a novel clamping technique. The clamping technique is realized by combining the loopy belief propagation message updating rule with the feedback from 3D rigid body registration. By using this clamping technique, the correct shape matching rate is increased significantly. Finally, we investigate 3D shape registration techniques based on the 3D shape matching result. Based on the point-to-point dense correspondences obtained from the 3D shape matching, a three-point based transformation estimation technique is combined with the RANdom SAmple Consensus (RANSAC) algorithm to obtain the inlier support set. The global registration approach is purely dependent on point-wise correspondences between two meshed surfaces. It has the advantage that the need for orientation initialisation is eliminated and that all shapes of spherical topology. The comparison of our MRF based 3D registration approach with a state-of-the-art registration algorithm, the first order ellipsoid template, is conducted in the experiments. These show dense correspondence for pairs of hippocampi from two different data sets, each of around 20 60+ year old healthy individuals

Cutset Sampling for Bayesian Networks

The paper presents a new sampling methodology for Bayesian networks that samples only a subset of variables and applies exact inference to the rest. Cutset sampling is a network structure-exploiting application of the Rao-Blackwellisation principle to sampling in Bayesian networks. It improves convergence by exploiting memory-based inference algorithms. It can also be viewed as an anytime approximation of the exact cutset-conditioning algorithm developed by Pearl. Cutset sampling can be implemented efficiently when the sampled variables constitute a loop-cutset of the Bayesian network and, more generally, when the induced width of the networks graph conditioned on the observed sampled variables is bounded by a constant w. We demonstrate empirically the benefit of this scheme on a range of benchmarks

Efficient inference in the transverse field Ising model

In this paper we introduce an approximate method to solve the quantum cavity equations for transverse field Ising models. The method relies on a projective approximation of the exact cavity distributions of imaginary time trajectories (paths). A key feature, novel in the context of similar algorithms, is the explicit separation of the classical and quantum parts of the distributions. Numerical simulations show accurate results in comparison with the sampled solution of the cavity equations, the exact diagonalization of the Hamiltonian (when possible) and other approximate inference methods in the literature. The computational complexity of this new algorithm scales linearly with the connectivity of the underlying lattice, enabling the study of highly connected networks, as the ones often encountered in quantum machine learning problems

Deformable shape matching

Deformable shape matching has become an important building block in academia as well as in industry. Given two three dimensional shapes A and B the deformation function f aligning A with B has to be found. The function is discretized by a set of corresponding point pairs. Unfortunately, the computation cost of a brute-force search of correspondences is exponential. Additionally, to be of any practical use the algorithm has to be able to deal with data coming directly from 3D scanner devices which suffers from acquisition problems like noise, holes as well as missing any information about topology. This dissertation presents novel solutions for solving shape matching: First, an algorithm estimating correspondences using a randomized search strategy is shown. Additionally, a planning step dramatically reducing the matching costs is incorporated. Using ideas of these both contributions, a method for matching multiple shapes at once is shown. The method facilitates the reconstruction of shape and motion from noisy data acquired with dynamic 3D scanners. Considering shape matching from another perspective a solution is shown using Markov Random Fields (MRF). Formulated as MRF, partial as well as full matches of a shape can be found. Here, belief propagation is utilized for inference computation in the MRF. Finally, an approach significantly reducing the space-time complexity of belief propagation for a wide spectrum of computer vision tasks is presented.Anpassung deformierbarer Formen ist zu einem wichtigen Baustein in der akademischen Welt sowie in der Industrie geworden. Gegeben zwei dreidimensionale Formen A und B, suchen wir nach einer Verformungsfunktion f, die die Deformation von A auf B abbildet. Die Funktion f wird durch eine Menge von korrespondierenden Punktepaaren diskretisiert. Leider sind die Berechnungskosten für eine Brute-Force-Suche dieser Korrespondenzen exponentiell. Um zusätzlich von einem praktischen Nutzen zu sein, muss der Suchalgorithmus in der Lage sein, mit Daten, die direkt aus 3D-Scanner kommen, umzugehen. Bedauerlicherweise leiden diese Daten unter Akquisitionsproblemen wie Rauschen, Löcher sowie fehlender Topologieinformation. In dieser Dissertation werden neue Lösungen für das Problem der Formanpassung präsentiert. Als erstes wird ein Algorithmus gezeigt, der die Korrespondenzen mittels einer randomisierten Suchstrategie schätzt. Zusätzlich wird anhand eines automatisch berechneten Schätzplanes die Geschwindigkeit der Suchstrategie verbessert. Danach wird ein Verfahren gezeigt, dass die Anpassung mehrerer Formen gleichzeitig bewerkstelligen kann. Diese Methode ermöglicht es, die Bewegung, sowie die eigentliche Struktur des Objektes aus verrauschten Daten, die mittels dynamischer 3D-Scanner aufgenommen wurden, zu rekonstruieren. Darauffolgend wird das Problem der Formanpassung aus einer anderen Perspektive betrachtet und als Markov-Netzwerk (MRF) reformuliert. Dieses ermöglicht es, die Formen auch stückweise aufeinander abzubilden. Die eigentliche Lösung wird mittels Belief Propagation berechnet. Schließlich wird ein Ansatz gezeigt, der die Speicher-Zeit-Komplexität von Belief Propagation für ein breites Spektrum von Computer-Vision Problemen erheblich reduziert