Swati Jain1, Qiyao Zhu2, Amiel S P Paz3, Tamar Schlick4. 1. Department of Chemistry, New York University, 1021 Silver, 100 Washington Square East, New York, NY 10003, USA. 2. Courant Institute of Mathematical Sciences, New York University, 251 Mercer Street, New York, NY 10012, USA. 3. NYU Shanghai, 1555 Century Avenue, Shanghai 200135, China; NYU-ECNU Center for Computational Chemistry, NYU Shanghai, 3663 Zhongshang Road North, Shanghai 200062, China. 4. Department of Chemistry, New York University, 1021 Silver, 100 Washington Square East, New York, NY 10003, USA; Courant Institute of Mathematical Sciences, New York University, 251 Mercer Street, New York, NY 10012, USA; NYU-ECNU Center for Computational Chemistry, NYU Shanghai, 3663 Zhongshang Road North, Shanghai 200062, China. Electronic address: schlick@nyu.edu.
Abstract
BACKGROUND: We re-evaluate our RNA-As-Graphs clustering approach, using our expanded graph library and new RNA structures, to identify potential RNA-like topologies for design. Our coarse-grained approach represents RNA secondary structures as tree and dual graphs, with vertices and edges corresponding to RNA helices and loops. The graph theoretical framework facilitates graph enumeration, partitioning, and clustering approaches to study RNA structure and its applications. METHODS: Clustering graph topologies based on features derived from graph Laplacian matrices and known RNA structures allows us to classify topologies into 'existing' or hypothetical, and the latter into, 'RNA-like' or 'non RNA-like' topologies. Here we update our list of existing tree graph topologies and RAG-3D database of atomic fragments to include newly determined RNA structures. We then use linear and quadratic regression, optionally with dimensionality reduction, to derive graph features and apply several clustering algorithms on our tree-graph library and recently expanded dual-graph library to classify them into the three groups. RESULTS: The unsupervised PAM and K-means clustering approaches correctly classify 72-77% of all existing graph topologies and 75-82% of newly added ones as RNA-like. For supervised k-NN clustering, the cross-validation accuracy ranges from 57 to 81%. CONCLUSIONS: Using linear regression with unsupervised clustering, or quadratic regression with supervised clustering, provides better accuracies than supervised/linear clustering. All accuracies are better than random, especially for newly added existing topologies, thus lending credibility to our approach. GENERAL SIGNIFICANCE: Our updated RAG-3D database and motif classification by clustering present new RNA substructures and RNA-like motifs as novel design candidates.
BACKGROUND: We re-evaluate our RNA-As-Graphs clustering approach, using our expanded graph library and new RNA structures, to identify potential RNA-like topologies for design. Our coarse-grained approach represents RNA secondary structures as tree and dual graphs, with vertices and edges corresponding to RNA helices and loops. The graph theoretical framework facilitates graph enumeration, partitioning, and clustering approaches to study RNA structure and its applications. METHODS: Clustering graph topologies based on features derived from graph Laplacian matrices and known RNA structures allows us to classify topologies into 'existing' or hypothetical, and the latter into, 'RNA-like' or 'non RNA-like' topologies. Here we update our list of existing tree graph topologies and RAG-3D database of atomic fragments to include newly determined RNA structures. We then use linear and quadratic regression, optionally with dimensionality reduction, to derive graph features and apply several clustering algorithms on our tree-graph library and recently expanded dual-graph library to classify them into the three groups. RESULTS: The unsupervised PAM and K-means clustering approaches correctly classify 72-77% of all existing graph topologies and 75-82% of newly added ones as RNA-like. For supervised k-NN clustering, the cross-validation accuracy ranges from 57 to 81%. CONCLUSIONS: Using linear regression with unsupervised clustering, or quadratic regression with supervised clustering, provides better accuracies than supervised/linear clustering. All accuracies are better than random, especially for newly added existing topologies, thus lending credibility to our approach. GENERAL SIGNIFICANCE: Our updated RAG-3D database and motif classification by clustering present new RNA substructures and RNA-like motifs as novel design candidates.
Authors: Tamar Schlick; Stephanie Portillo-Ledesma; Christopher G Myers; Lauren Beljak; Justin Chen; Sami Dakhel; Daniel Darling; Sayak Ghosh; Joseph Hall; Mikaeel Jan; Emily Liang; Sera Saju; Mackenzie Vohr; Chris Wu; Yifan Xu; Eva Xue Journal: Annu Rev Biophys Date: 2021-02-19 Impact factor: 12.981