Delta: a Toolset for the Structural Analysis of Biological Sequences - PowerPoint PPT Presentation

Motivation The Delta Toolset Applications Summary Delta: a Toolset for the Structural Analysis of Biological Sequences on a 3D Triangular Lattice Minghui Jiang Martin Mayne Joel Gillespie Department of Computer Science, Utah State University International Symposium on Bioinformatics Research and Applications, Atlanta, Georgia, May 7–10, 2007 Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation The Delta Toolset Applications Summary Outline Motivation 1 The Delta Toolset 2 Structure Representation Visualization and Manipulation Folding Simulation 3 Applications Prediction of RNA Secondary Structures Validation and Visualization of RNA Secondary Structures Thermodynamic Stability Analysis of RNAs Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation The Delta Toolset Applications Summary Outline Motivation 1 The Delta Toolset 2 Structure Representation Visualization and Manipulation Folding Simulation 3 Applications Prediction of RNA Secondary Structures Validation and Visualization of RNA Secondary Structures Thermodynamic Stability Analysis of RNAs Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation The Delta Toolset Applications Summary Protein folding in HP model 20 types of amino acids: hydrophobic (H) or hydrophilic (P). A sequence folds on a lattice: each element occupies a unique lattice point; consecutive elements in the sequence occupy adjacent lattice points. Optimization: to maximize the number of H-H contacts. Extensively studied: folding kinetics simulation, computational complexities, approximation algorithms, alternative lattices. Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation The Delta Toolset Applications Summary An example on 2D hexagonal lattice Minghui Jiang and Binhai Zhu. Protein folding on the hexagonal lattice in the HP model. Journal of Bioinformatics and Computational Biology , 3(1):19–34, 2005. Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation The Delta Toolset Applications Summary RNA folding Previous work Dynamic programming. Secondary structure (base pairs) first, tertiary structure next. Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation The Delta Toolset Applications Summary RNA folding Previous work Dynamic programming. Secondary structure (base pairs) first, tertiary structure next. Our approach: RNA folding on a 3D triangular lattice. Simulate tertiary structure directly, then derive secondary structure. Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation The Delta Toolset Applications Summary RNA folding Previous work Dynamic programming. Secondary structure (base pairs) first, tertiary structure next. Our approach: RNA folding on a 3D triangular lattice. Simulate tertiary structure directly, then derive secondary structure. Two advantages: The predicted structure is always realizable in 3D. Arbitrary pseudoknots. Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation The Delta Toolset Applications Summary RNA folding Previous work Dynamic programming. Secondary structure (base pairs) first, tertiary structure next. Our approach: RNA folding on a 3D triangular lattice. Simulate tertiary structure directly, then derive secondary structure. Two advantages: The predicted structure is always realizable in 3D. Arbitrary pseudoknots. 3D triangular lattice is non-trivial: the Delta toolset. Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation Structure Representation The Delta Toolset Visualization and Manipulation Applications Folding Simulation Summary Outline Motivation 1 The Delta Toolset 2 Structure Representation Visualization and Manipulation Folding Simulation 3 Applications Prediction of RNA Secondary Structures Validation and Visualization of RNA Secondary Structures Thermodynamic Stability Analysis of RNAs Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation Structure Representation The Delta Toolset Visualization and Manipulation Applications Folding Simulation Summary Outline Motivation 1 The Delta Toolset 2 Structure Representation Visualization and Manipulation Folding Simulation 3 Applications Prediction of RNA Secondary Structures Validation and Visualization of RNA Secondary Structures Thermodynamic Stability Analysis of RNAs Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation Structure Representation The Delta Toolset Visualization and Manipulation Applications Folding Simulation Summary 3D triangular lattice y z y x x √ 2 z z = 0 1 z = 1 1 A closest cubic packing of spheres. 12 neighbors on three square lattices in parallel planes. Better than cubic lattice: denser; no parity constraint. Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation Structure Representation The Delta Toolset Visualization and Manipulation Applications Folding Simulation Summary Representation of a structure 3 primary axes and 3 auxiliary axes: x y z � � � u = � x + � z v = � y + � z w = � x + � y + � z � � � External: a turn sequence over the alphabet { U , V , W , X , Y , Z , u , v , w , x , y , z } Internal: an array of ( x , y , z ) coordinates and a hashtable (collision detection in expected constant time). Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation Structure Representation The Delta Toolset Visualization and Manipulation Applications Folding Simulation Summary Outline Motivation 1 The Delta Toolset 2 Structure Representation Visualization and Manipulation Folding Simulation 3 Applications Prediction of RNA Secondary Structures Validation and Visualization of RNA Secondary Structures Thermodynamic Stability Analysis of RNAs Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation Structure Representation The Delta Toolset Visualization and Manipulation Applications Folding Simulation Summary Balls and sticks Zooming, rotation, interactive manipulation, . . . Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation Structure Representation The Delta Toolset Visualization and Manipulation Applications Folding Simulation Summary Manipulation of structures: flip moves Flip moves are local: constant time per move Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation Structure Representation The Delta Toolset Visualization and Manipulation Applications Folding Simulation Summary Manipulation of structures: pivot moves Pivot moves are global: Ω( n ) time per move on average. Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation Structure Representation The Delta Toolset Visualization and Manipulation Applications Folding Simulation Summary Manipulation of structures: pull moves Introduced by Lesh et al. for protein folding on square lattice. Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation Structure Representation The Delta Toolset Visualization and Manipulation Applications Folding Simulation Summary We chose pull moves Almost-local: each random move relocates only a small number of elements on average sequence length 32 64 128 256 512 average # of relocated elements 2.4 3.8 4.1 3.4 3.5 standard deviation 1.3 2.7 3.2 2.0 2.4 Reversible: A → B ⇐ ⇒ B → A Complete: A � B Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice

Motivation Structure Representation The Delta Toolset Visualization and Manipulation Applications Folding Simulation Summary Outline Motivation 1 The Delta Toolset 2 Structure Representation Visualization and Manipulation Folding Simulation 3 Applications Prediction of RNA Secondary Structures Validation and Visualization of RNA Secondary Structures Thermodynamic Stability Analysis of RNAs Minghui Jiang, Martin Mayne, Joel Gillespie Delta: a Toolset for Structural Analysis on a 3D Triangular Lattice