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      Network enhancement as a general method to denoise weighted biological networks

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          Abstract

          Networks are ubiquitous in biology where they encode connectivity patterns at all scales of organization, from molecular to the biome. However, biological networks are noisy due to the limitations of measurement technology and inherent natural variation, which can hamper discovery of network patterns and dynamics. We propose Network Enhancement (NE), a method for improving the signal-to-noise ratio of undirected, weighted networks. NE uses a doubly stochastic matrix operator that induces sparsity and provides a closed-form solution that increases spectral eigengap of the input network. As a result, NE removes weak edges, enhances real connections, and leads to better downstream performance. Experiments show that NE improves gene–function prediction by denoising tissue-specific interaction networks, alleviates interpretation of noisy Hi-C contact maps from the human genome, and boosts fine-grained identification accuracy of species. Our results indicate that NE is widely applicable for denoising biological networks.

          Abstract

          Technical noise in experiments is unavoidable, but it introduces inaccuracies into the biological networks we infer from the data. Here, the authors introduce a diffusion-based method for denoising undirected, weighted networks, and show that it improves the performances of downstream analyses.

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          Fast unfolding of communities in large networks

          We propose a simple method to extract the community structure of large networks. Our method is a heuristic method that is based on modularity optimization. It is shown to outperform all other known community detection method in terms of computation time. Moreover, the quality of the communities detected is very good, as measured by the so-called modularity. This is shown first by identifying language communities in a Belgian mobile phone network of 2.6 million customers and by analyzing a web graph of 118 million nodes and more than one billion links. The accuracy of our algorithm is also verified on ad-hoc modular networks. .
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            A global genetic interaction network maps a wiring diagram of cellular function.

            We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell.
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              Genome architecture: domain organization of interphase chromosomes.

              The architecture of interphase chromosomes is important for the regulation of gene expression and genome maintenance. Chromosomes are linearly segmented into hundreds of domains with different protein compositions. Furthermore, the spatial organization of chromosomes is nonrandom and is characterized by many local and long-range contacts among genes and other sequence elements. A variety of genome-wide mapping techniques have made it possible to chart these properties at high resolution. Combined with microscopy and computational modeling, the results begin to yield a more coherent picture that integrates linear and three-dimensional (3D) views of chromosome organization in relation to gene regulation and other nuclear functions. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                serafim@cs.stanford.edu
                jure@cs.stanford.edu
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                6 August 2018
                6 August 2018
                2018
                : 9
                : 3108
                Affiliations
                [1 ]ISNI 0000000419368956, GRID grid.168010.e, Department of Computer Science, , Stanford University, ; 353 Serra Mall, Stanford, 94305 CA USA
                [2 ]ISNI 0000000419368956, GRID grid.168010.e, Department of Physics, , Stanford University, ; 382 Via Pueblo Mall, Stanford, 94305 CA USA
                [3 ]ISNI 0000000419368956, GRID grid.168010.e, Department of Electrical Engineering, , Stanford University, ; 350 Serra Mall, Stanford, 94305 CA USA
                [4 ]ISNI 0000000419368956, GRID grid.168010.e, Department of Biomedical Data Science, , Stanford University, ; 1265 Welch Road, Stanford, 94305 CA USA
                [5 ]Chan Zuckerberg Biohub, 499 Illinois St, San Francisco, 94158 CA USA
                [6 ]ISNI 0000 0004 0507 3954, GRID grid.185669.5, Present Address: Illumina Inc, ; 499 Illinois Street, San Francisco, 94158 CA USA
                Article
                5469
                10.1038/s41467-018-05469-x
                6078978
                30082777
                88fd8da9-f699-40c0-a725-fa2f03de73e1
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 October 2017
                : 3 July 2018
                Funding
                Funded by: National Institutes of Health/National Human Genome Research Institute T32 HG-000044, Chan Zuckerberg Initiative, and Grant Number U01FD004979 from the FDA, which supports the UCSF-Stanford Center of Excellence in Regulatory Sciences and Innovation.
                Funded by: NSF, NIH BD2K, DARPA SIMPLEX, Stanford Data Science Initiative, Chan Zuckerberg Biohub.
                Funded by: Stanford Graduate Fellowship, NSF DMS 1712800 Grant, and the Stanford Discovery Innovation Fund.
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