miniMDS: 3D structural inference from high-resolution Hi-C data

Motivation: Recent experiments have provided Hi‐C data at resolution as high as 1 kbp. However, 3D structural inference from high‐resolution Hi‐C datasets is often computationally unfeasible using existing methods. Results: We have developed miniMDS, an approximation of multidimensional scaling (MDS) that partitions a Hi‐C dataset, performs high‐resolution MDS separately on each partition, and then reassembles the partitions using low‐resolution MDS. miniMDS is faster, more accurate, and uses less memory than existing methods for inferring the human genome at high resolution (10 kbp). Availability and implementation: A Python implementation of miniMDS is available on GitHub: https://github.com/seqcode/miniMDS. Contact: mahony@psu.edu Supplementary information: Supplementary data are available at Bioinformatics online.

[1]  A. Lesne,et al.  3D genome reconstruction from chromosomal contacts , 2014, Nature Methods.

[2]  Ming Hu,et al.  Bayesian Inference of Spatial Organizations of Chromosomes , 2013, PLoS Comput. Biol..

[3]  Jinbo Xu,et al.  Inferential modeling of 3D chromatin structure , 2015, Nucleic acids research.

[4]  William Stafford Noble,et al.  A Three-Dimensional Model of the Yeast Genome , 2010, Nature.

[5]  Dariusz Plewczynski,et al.  An integrated 3-Dimensional Genome Modeling Engine for data-driven simulation of spatial genome organization , 2016, Genome research.

[6]  Gaël Varoquaux,et al.  Scikit-learn: Machine Learning in Python , 2011, J. Mach. Learn. Res..

[7]  Kim-Chuan Toh,et al.  3D Chromosome Modeling with Semi-Definite Programming and Hi-C Data , 2013, J. Comput. Biol..

[8]  Badri Adhikari,et al.  Chromosome3D: reconstructing three-dimensional chromosomal structures from Hi-C interaction frequency data using distance geometry simulated annealing , 2016, BMC Genomics.

[9]  Brian J. Beliveau,et al.  Spatial organization of chromatin domains and compartments in single chromosomes , 2016, Science.

[10]  W. Kabsch.  A solution for the best rotation to relate two sets of vectors , 1976 .

[11]  Daniel Ruiz,et al.  A Fast Algorithm for Matrix Balancing , 2013, Web Information Retrieval and Linear Algebra Algorithms.

[12]  Liisa Holm,et al.  Advances and pitfalls of protein structural alignment. , 2009, Current opinion in structural biology.

[13]  Chenchen Zou,et al.  HSA: integrating multi-track Hi-C data for genome-scale reconstruction of 3D chromatin structure , 2016, Genome Biology.

[14]  Jianlin Cheng,et al.  Large-scale reconstruction of 3D structures of human chromosomes from chromosomal contact data , 2014, Nucleic acids research.

[15]  Mathieu Blanchette,et al.  Three-dimensional modeling of chromatin structure from interaction frequency data using Markov chain Monte Carlo sampling , 2011, BMC Bioinformatics.

[16]  L. Mirny,et al.  Iterative Correction of Hi-C Data Reveals Hallmarks of Chromosome Organization , 2012, Nature Methods.

[17]  Shili Lin,et al.  Impact of data resolution on three-dimensional structure inference methods , 2016, BMC Bioinformatics.

[18]  Neva C. Durand,et al.  A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping , 2014, Cell.

[19]  Nils Blüthgen,et al.  Reciprocal insulation analysis of Hi-C data shows that TADs represent a functionally but not structurally privileged scale in the hierarchical folding of chromosomes , 2017, Genome research.

[20]  William Stafford Noble,et al.  A statistical approach for inferring the 3D structure of the genome , 2014, Bioinform..

[21]  Jesse R. Dixon,et al.  Topological Domains in Mammalian Genomes Identified by Analysis of Chromatin Interactions , 2012, Nature.

[22]  Marc A Marti-Renom,et al.  Genome structure determination via 3C-based data integration by the Integrative Modeling Platform. , 2012, Methods.

[23]  I. Amit,et al.  Comprehensive mapping of long range interactions reveals folding principles of the human genome , 2011 .

[24]  John Platt,et al.  FastMap, MetricMap, and Landmark MDS are all Nystrom Algorithms , 2005, AISTATS.

[25]  Stephen Smale,et al.  Functional organization of the human 4D Nucleome , 2015, Proceedings of the National Academy of Sciences.