A signal transduction score flow algorithm for cyclic cellular pathway analysis, which combines transcriptome and ChIP-seq data.

Determination of cell signalling behaviour is crucial for understanding the physiological response to a specific stimulus or drug treatment. Current approaches for large-scale data analysis do not effectively incorporate critical topological information provided by the signalling network. We herein describe a novel model- and data-driven hybrid approach, or signal transduction score flow algorithm, which allows quantitative visualization of cyclic cell signalling pathways that lead to ultimate cell responses such as survival, migration or death. This score flow algorithm translates signalling pathways as a directed graph and maps experimental data, including negative and positive feedbacks, onto gene nodes as scores, which then computationally traverse the signalling pathway until a pre-defined biological target response is attained. Initially, experimental data-driven enrichment scores of the genes were computed in a pathway, then a heuristic approach was applied using the gene score partition as a solution for protein node stoichiometry during dynamic scoring of the pathway of interest. Incorporation of a score partition during the signal flow and cyclic feedback loops in the signalling pathway significantly improves the usefulness of this model, as compared to other approaches. Evaluation of the score flow algorithm using both transcriptome and ChIP-seq data-generated signalling pathways showed good correlation with expected cellular behaviour on both KEGG and manually generated pathways. Implementation of the algorithm as a Cytoscape plug-in allows interactive visualization and analysis of KEGG pathways as well as user-generated and curated Cytoscape pathways. Moreover, the algorithm accurately predicts gene-level and global impacts of single or multiple in silico gene knockouts.

Multilevel segmentation of histopathological images using cooccurrence of tissue objects.

This paper presents a new approach for unsupervised segmentation of histopathological tissue images. This approach has two main contributions. First, it introduces a new set of high-level texture features to represent the prior knowledge of spatial organization of the tissue components. These texture features are defined on the tissue components, which are approximately represented by tissue objects, and quantify the frequency of two component types being cooccurred in a particular spatial relationship. As they are defined on components, rather than on image pixels, these object cooccurrence features are expected to be less vulnerable to noise and variations that are typically observed at the pixel level of tissue images. Second, it proposes to obtain multiple segmentations by multilevel partitioning of a graph constructed on the tissue objects and combine them by an ensemble function. This multilevel graph partitioning algorithm introduces randomization in graph construction and refinements in its multilevel scheme to increase diversity of individual segmentations, and thus, improve the final result. The experiments on 200 colon tissue images reveal that the proposed approach--the object cooccurrence features together with the multilevel segmentation algorithm--is effective to obtain high-quality results. The experiments also show that it improves the segmentation results compared to the previous approaches.

A fast neural-network algorithm for VLSI cell placement.

Cell placement is an important phase of current VLSI circuit design styles such as standard cell, gate array, and Field Programmable Gate Array (FPGA). Although nondeterministic algorithms such as Simulated Annealing (SA) were successful in solving this problem, they are known to be slow. In this paper, a neural network algorithm is proposed that produces solutions as good as SA in substantially less time. This algorithm is based on Mean Field Annealing (MFA) technique, which was successfully applied to various combinatorial optimization problems. A MFA formulation for the cell placement problem is derived which can easily be applied to all VLSI design styles. To demonstrate that the proposed algorithm is applicable in practice, a detailed formulation for the FPGA design style is derived, and the layouts of several benchmark circuits are generated. The performance of the proposed cell placement algorithm is evaluated in comparison with commercial automated circuit design software Xilinx Automatic Place and Route (APR) which uses SA technique. Performance evaluation is conducted using ACM/SIGDA Design Automation benchmark circuits. Experimental results indicate that the proposed MFA algorithm produces comparable results with APR. However, MFA is almost 20 times faster than APR on the average.