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Title: IMG-ABC. A knowledge base to fuel discovery of biosynthetic gene clusters and novel secondary metabolites

Abstract

In the discovery of secondary metabolites, analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of computational platforms that enable such a systematic approach on a large scale. In this work, we present IMG-ABC (https://img.jgi.doe.gov/abc), an atlas of biosynthetic gene clusters within the Integrated Microbial Genomes (IMG) system, which is aimed at harnessing the power of “big” genomic data for discovering small molecules. IMG-ABC relies on IMG’s comprehensive integrated structural and functional genomic data for the analysis of biosynthetic gene clusters (BCs) and associated secondary metabolites (SMs). SMs and BCs serve as the two main classes of objects in IMG-ABC, each with a rich collection of attributes. A unique feature of IMG-ABC is the incorporation of both experimentally validated and computationally predicted BCs in genomes as well as metagenomes, thus identifying BCs in uncultured populations and rare taxa. We demonstrate the strength of IMG-ABC’s focused integrated analysis tools in enabling the exploration of microbial secondary metabolism on a global scale, through the discovery of phenazine-producing clusters for the first time in lphaproteobacteria. IMG-ABC strives to fill the long-existent void of resources for computational exploration of the secondary metabolism universe; its underlying scalablemore » framework enables traversal of uncovered phylogenetic and chemical structure space, serving as a doorway to a new era in the discovery of novel molecules. IMG-ABC is the largest publicly available database of predicted and experimental biosynthetic gene clusters and the secondary metabolites they produce. The system also includes powerful search and analysis tools that are integrated with IMG’s extensive genomic/metagenomic data and analysis tool kits. As new research on biosynthetic gene clusters and secondary metabolites is published and more genomes are sequenced, IMG-ABC will continue to expand, with the goal of becoming an essential component of any bioinformatic exploration of the secondary metabolism world.« less

Authors:
 [1];  [2];  [2];  [2];  [2];  [2];  [2];  [1];  [3];  [3];  [1];  [2];  [1];  [1]
  1. DOE Joint Genome Institute, Walnut Creek, CA (United States)
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  3. Univ. of California, San Francisco, San Francisco, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1215425
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
mBio (Online)
Additional Journal Information:
Journal Name: mBio (Online); Journal Volume: 6; Journal Issue: 4; Journal ID: ISSN 2150-7511
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 96 KNOWLEDGE MANAGEMENT AND PRESERVATION

Citation Formats

Hadjithomas, Michalis, Chen, I-Min Amy, Chu, Ken, Ratner, Anna, Palaniappan, Krishna, Szeto, Ernest, Huang, Jinghua, Reddy, T. B. K., Cimermančič, Peter, Fischbach, Michael A., Ivanova, Natalia N., Markowitz, Victor M., Kyrpides, Nikos C., and Pati, Amrita. IMG-ABC. A knowledge base to fuel discovery of biosynthetic gene clusters and novel secondary metabolites. United States: N. p., 2015. Web. doi:10.1128/mBio.00932-15.
Hadjithomas, Michalis, Chen, I-Min Amy, Chu, Ken, Ratner, Anna, Palaniappan, Krishna, Szeto, Ernest, Huang, Jinghua, Reddy, T. B. K., Cimermančič, Peter, Fischbach, Michael A., Ivanova, Natalia N., Markowitz, Victor M., Kyrpides, Nikos C., & Pati, Amrita. IMG-ABC. A knowledge base to fuel discovery of biosynthetic gene clusters and novel secondary metabolites. United States. doi:10.1128/mBio.00932-15.
Hadjithomas, Michalis, Chen, I-Min Amy, Chu, Ken, Ratner, Anna, Palaniappan, Krishna, Szeto, Ernest, Huang, Jinghua, Reddy, T. B. K., Cimermančič, Peter, Fischbach, Michael A., Ivanova, Natalia N., Markowitz, Victor M., Kyrpides, Nikos C., and Pati, Amrita. Tue . "IMG-ABC. A knowledge base to fuel discovery of biosynthetic gene clusters and novel secondary metabolites". United States. doi:10.1128/mBio.00932-15. https://www.osti.gov/servlets/purl/1215425.
@article{osti_1215425,
title = {IMG-ABC. A knowledge base to fuel discovery of biosynthetic gene clusters and novel secondary metabolites},
author = {Hadjithomas, Michalis and Chen, I-Min Amy and Chu, Ken and Ratner, Anna and Palaniappan, Krishna and Szeto, Ernest and Huang, Jinghua and Reddy, T. B. K. and Cimermančič, Peter and Fischbach, Michael A. and Ivanova, Natalia N. and Markowitz, Victor M. and Kyrpides, Nikos C. and Pati, Amrita},
abstractNote = {In the discovery of secondary metabolites, analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of computational platforms that enable such a systematic approach on a large scale. In this work, we present IMG-ABC (https://img.jgi.doe.gov/abc), an atlas of biosynthetic gene clusters within the Integrated Microbial Genomes (IMG) system, which is aimed at harnessing the power of “big” genomic data for discovering small molecules. IMG-ABC relies on IMG’s comprehensive integrated structural and functional genomic data for the analysis of biosynthetic gene clusters (BCs) and associated secondary metabolites (SMs). SMs and BCs serve as the two main classes of objects in IMG-ABC, each with a rich collection of attributes. A unique feature of IMG-ABC is the incorporation of both experimentally validated and computationally predicted BCs in genomes as well as metagenomes, thus identifying BCs in uncultured populations and rare taxa. We demonstrate the strength of IMG-ABC’s focused integrated analysis tools in enabling the exploration of microbial secondary metabolism on a global scale, through the discovery of phenazine-producing clusters for the first time in lphaproteobacteria. IMG-ABC strives to fill the long-existent void of resources for computational exploration of the secondary metabolism universe; its underlying scalable framework enables traversal of uncovered phylogenetic and chemical structure space, serving as a doorway to a new era in the discovery of novel molecules. IMG-ABC is the largest publicly available database of predicted and experimental biosynthetic gene clusters and the secondary metabolites they produce. The system also includes powerful search and analysis tools that are integrated with IMG’s extensive genomic/metagenomic data and analysis tool kits. As new research on biosynthetic gene clusters and secondary metabolites is published and more genomes are sequenced, IMG-ABC will continue to expand, with the goal of becoming an essential component of any bioinformatic exploration of the secondary metabolism world.},
doi = {10.1128/mBio.00932-15},
journal = {mBio (Online)},
number = 4,
volume = 6,
place = {United States},
year = {2015},
month = {7}
}

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