{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T20:17:30Z","timestamp":1773951450528,"version":"3.50.1"},"reference-count":132,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61772313"],"award-info":[{"award-number":["61772313"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Young Scholars Program of Shandong University","award":["2015WLJH19"],"award-info":[{"award-number":["2015WLJH19"]}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2018IM020200"],"award-info":[{"award-number":["2018IM020200"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002733"],"award-info":[{"award-number":["UL1TR002733"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["#ACI-1548562"],"award-info":[{"award-number":["#ACI-1548562"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,22]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Together with various hosts and environments, ubiquitous microbes interact closely with each other forming an intertwined system or community. Of interest, shifts of the relationships between microbes and their hosts or environments are associated with critical diseases and ecological changes. While advances in high-throughput Omics technologies offer a great opportunity for understanding the structures and functions of microbiome, it is still challenging to analyse and interpret the omics data. Specifically, the heterogeneity and diversity of microbial communities, compounded with the large size of the datasets, impose a tremendous challenge to mechanistically elucidate the complex communities. Fortunately, network analyses provide an efficient way to tackle this problem, and several network approaches have been proposed to improve this understanding recently. Here, we systemically illustrate these network theories that have been used in biological and biomedical research. Then, we review existing network modelling methods of microbial studies at multiple layers from metagenomics to metabolomics and further to multi-omics. Lastly, we discuss the limitations of present studies and provide a perspective for further directions in support of the understanding of microbial communities.<\/jats:p>","DOI":"10.1093\/bib\/bbaa005","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T20:08:47Z","timestamp":1578600527000},"page":"1639-1655","source":"Crossref","is-referenced-by-count":83,"title":["Network analyses in microbiome based on high-throughput multi-omics data"],"prefix":"10.1093","volume":"22","author":[{"given":"Zhaoqian","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, the Ohio State University, Columbus, OH 43210, USA"}]},{"given":"Anjun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, the Ohio State University, Columbus, OH 43210, USA"}]},{"given":"Ewy","family":"Math\u00e9","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, the Ohio State University, Columbus, OH 43210, USA"}]},{"given":"Marlena","family":"Merling","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, the Ohio State University, Columbus, OH 43210, USA"}]},{"given":"Qin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, the Ohio State University, Columbus, OH 43210, USA"}]},{"given":"Bingqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, the Ohio State University, Columbus, OH 43210, USA"}]}],"member":"286","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"key":"2021032400074182200_ref1","doi-asserted-by":"crossref","first-page":"4162","DOI":"10.1172\/JCI78366","article-title":"The microbiome revolution","volume":"124","author":"Blaser","year":"2014","journal-title":"J Clin Invest"},{"key":"2021032400074182200_ref2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1146\/annurev.mi.39.100185.001541","article-title":"Measurement of in situ activities of nonphotosynthetic microorganisms in aquatic and terrestrial habitats","volume":"39","author":"Staley","year":"1985","journal-title":"Annu Rev Microbiol"},{"key":"2021032400074182200_ref3","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1038\/sj.embor.7400812","article-title":"Who are we? Indigenous microbes and the ecology of human diseases","volume":"7","author":"Blaser","year":"2006","journal-title":"EMBO Rep"},{"key":"2021032400074182200_ref4","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nature11234","article-title":"Structure, function and diversity of the healthy human microbiome","volume":"486","author":"Huttenhower","year":"2012","journal-title":"Nature"},{"key":"2021032400074182200_ref5","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/ismej.2008.58","article-title":"Microbial contributions to climate change through carbon cycle feedbacks","volume":"2","author":"Bardgett","year":"2008","journal-title":"ISME J"},{"key":"2021032400074182200_ref6","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1094\/PHYTO-02-16-0058-FI","article-title":"Microbiome networks: a systems framework for identifying candidate microbial assemblages for disease management","volume":"106","author":"Poudel","year":"2016","journal-title":"Phytopathology"},{"key":"2021032400074182200_ref7","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1007\/s000180050021","article-title":"Antibiotic resistance in microbes","volume":"56","author":"Mazel","year":"1999","journal-title":"Cell Mol Life Sci C"},{"key":"2021032400074182200_ref8","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/nature09944","article-title":"Enterotypes of the human gut microbiome","volume":"473","author":"Arumugam","year":"2011","journal-title":"Nature"},{"key":"2021032400074182200_ref9","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/s41598-018-37143-z","article-title":"The gut microbiota heterogeneity and assembly changes associated with the IBD","volume":"9","author":"Sun","year":"2019","journal-title":"Sci Rep"},{"key":"2021032400074182200_ref10","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrg1272","article-title":"Network biology: understanding the cell\u2019s functional organization","volume":"5","author":"Barabasi","year":"2004","journal-title":"Nat Rev Genet"},{"key":"2021032400074182200_ref11","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1146\/annurev.genet.38.072902.091216","article-title":"Metagenomics: genomic analysis of microbial communities","volume":"38","author":"Riesenfeld","year":"2004","journal-title":"Annu Rev Genet"},{"key":"2021032400074182200_ref12","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.mimet.2013.08.011","article-title":"High throughput sequencing methods and analysis for microbiome research","volume":"95","author":"Di Bella","year":"2013","journal-title":"J Microbiol Methods"},{"key":"2021032400074182200_ref13","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1038\/ismej.2011.158","article-title":"The activity level of a microbial community function can be predicted from its metatranscriptome","volume":"6","author":"Helbling","year":"2012","journal-title":"ISME J"},{"key":"2021032400074182200_ref14","doi-asserted-by":"crossref","first-page":"e02288","DOI":"10.1128\/mBio.02288-14","article-title":"High-throughput metagenomic technologies for complex microbial community analysis: open and closed formats","volume":"6","author":"Zhou","year":"2015","journal-title":"MBio"},{"key":"2021032400074182200_ref15","doi-asserted-by":"crossref","first-page":"BBI","DOI":"10.4137\/BBI.S34610","article-title":"Use of metatranscriptomics in microbiome research","volume":"10","author":"Bashiardes","year":"2016","journal-title":"Bioinform Biol Insights"},{"key":"2021032400074182200_ref16","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.mib.2009.03.004","article-title":"Microbial community proteomics: elucidating the catalysts and metabolic mechanisms that drive the Earth\u2019s biogeochemical cycles","volume":"12","author":"Wilmes","year":"2009","journal-title":"Curr Opin Microbiol"},{"key":"2021032400074182200_ref17","doi-asserted-by":"crossref","first-page":"391","DOI":"10.2174\/138920211797248619","article-title":"Microbial metabolomics","volume":"12","author":"Tang","year":"2011","journal-title":"Curr Genomics"},{"key":"2021032400074182200_ref18","doi-asserted-by":"crossref","first-page":"16180","DOI":"10.1038\/nmicrobiol.2016.180","article-title":"Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes","volume":"2","author":"Heintz-Buschart","year":"2017","journal-title":"Nat Microbiol"},{"key":"2021032400074182200_ref19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nature11209","article-title":"A framework for human microbiome research","volume":"486","author":"Meth\u00e9","year":"2012","journal-title":"Nature"},{"key":"2021032400074182200_ref20","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/s41586-019-1238-8","article-title":"The Integrative human microbiome project","volume":"569","author":"Integrative","year":"2019","journal-title":"Nature"},{"key":"2021032400074182200_ref21","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.chom.2014.08.014","article-title":"The Integrative human microbiome project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease","volume":"16","author":"Integrative","year":"2014","journal-title":"Cell Host Microbe"},{"key":"2021032400074182200_ref22","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature08821","article-title":"A human gut microbial gene catalogue established by metagenomic sequencing","volume":"464","author":"Qin","year":"2010","journal-title":"Nature"},{"key":"2021032400074182200_ref23","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3389\/fmicb.2018.00296","article-title":"The genome-scale integrated networks in microorganisms","volume":"9","author":"Hao","year":"2018","journal-title":"Front Microbiol"},{"key":"2021032400074182200_ref24","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.tim.2016.11.008","article-title":"Disentangling interactions in the microbiome: a network perspective","volume":"25","author":"Layeghifard","year":"2017","journal-title":"Trends Microbiol"},{"key":"2021032400074182200_ref25","volume-title":"Evolution of Networks: From Biological Nets to the Internet and WWW","author":"Dorogovtsev","year":"2013"},{"key":"2021032400074182200_ref26","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/35065725","article-title":"Exploring complex networks","volume":"410","author":"Strogatz","year":"2001","journal-title":"Nature"},{"key":"2021032400074182200_ref27","doi-asserted-by":"crossref","first-page":"D394","DOI":"10.1093\/nar\/gkj156","article-title":"RegulonDB (version 5.0): Escherichia coli K-12 transcriptional regulatory network, operon organization, and growth conditions","volume":"34","author":"Salgado","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"2021032400074182200_ref28","doi-asserted-by":"crossref","first-page":"tr5","DOI":"10.1126\/scisignal.2001965","article-title":"Introduction to network analysis in systems biology","volume":"4","author":"Ma\u2019ayan","year":"2011","journal-title":"Sci Signal"},{"key":"2021032400074182200_ref29","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1098\/rstb.2005.1725","article-title":"Defining operational taxonomic units using DNA barcode data","volume":"360","author":"Blaxter","year":"2005","journal-title":"Philos Trans R Soc B Biol Sci"},{"key":"2021032400074182200_ref30","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1126\/science.286.5439.509","article-title":"Emergence of scaling in random networks","volume":"286","author":"Barab\u00e1si","year":"1999","journal-title":"Science (80-.)."},{"key":"2021032400074182200_ref31","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1038\/ismej.2015.261","article-title":"Geographic patterns of co-occurrence network topological features for soil microbiota at continental scale in eastern China","volume":"10","author":"Ma","year":"2016","journal-title":"ISME J"},{"key":"2021032400074182200_ref32","doi-asserted-by":"crossref","first-page":"e1002352","DOI":"10.1371\/journal.pbio.1002352","article-title":"Microbial hub taxa link host and abiotic factors to plant microbiome variation","volume":"14","author":"Agler","year":"2016","journal-title":"PLoS Biol"},{"key":"2021032400074182200_ref33","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1752-0509-3-102","article-title":"How to identify essential genes from molecular networks?","volume":"3","author":"Rio","year":"2009","journal-title":"BMC Syst Biol"},{"key":"2021032400074182200_ref34","doi-asserted-by":"crossref","first-page":"1289259","DOI":"10.1155\/2017\/1289259","article-title":"Drug target protein-protein interaction networks: a systematic perspective","volume":"2017","author":"Feng","year":"2017","journal-title":"Biomed Res Int"},{"key":"2021032400074182200_ref35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/pmic.200500209","article-title":"Virtual identification of essential proteins within the protein interaction network of yeast","volume":"6","author":"Estrada","year":"2006","journal-title":"Proteomics"},{"key":"2021032400074182200_ref36","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/nature03288","article-title":"Functional cartography of complex metabolic networks","volume":"433","author":"Guimera","year":"2005","journal-title":"Nature"},{"key":"2021032400074182200_ref37","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/msb4100129","article-title":"Network-based prediction of protein function","volume":"3","author":"Sharan","year":"2007","journal-title":"Mol Syst Biol"},{"key":"2021032400074182200_ref38","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1038\/s41467-019-09186-x","article-title":"Network-based prediction of drug combinations","volume":"10","author":"Cheng","year":"2019","journal-title":"Nat Commun"},{"key":"2021032400074182200_ref39","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1093\/bioinformatics\/btl533","article-title":"An algorithm for modularity analysis of directed and weighted biological networks based on edge-betweenness centrality","volume":"22","author":"Yoon","year":"2006","journal-title":"Bioinformatics"},{"key":"2021032400074182200_ref40","doi-asserted-by":"crossref","first-page":"26113","DOI":"10.1103\/PhysRevE.69.026113","article-title":"Finding and evaluating community structure in networks","volume":"69","author":"Newman","year":"2004","journal-title":"Phys. Rev. E"},{"key":"2021032400074182200_ref41","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/bioinformatics\/bth167","article-title":"Decomposition of metabolic network into functional modules based on the global connectivity structure of reaction graph","volume":"20","author":"Ma","year":"2004","journal-title":"Bioinformatics"},{"key":"2021032400074182200_ref42","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/1752-0509-4-74","article-title":"Co-expression module analysis reveals biological processes, genomic gain, and regulatory mechanisms associated with breast cancer progression","volume":"4","author":"Shi","year":"2010","journal-title":"BMC Syst Biol"},{"key":"2021032400074182200_ref43","doi-asserted-by":"crossref","first-page":"13356","DOI":"10.1073\/pnas.2235868100","article-title":"Developmental gene regulatory network architecture across 500 million years of echinoderm evolution","volume":"100","author":"Hinman","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021032400074182200_ref44","doi-asserted-by":"crossref","first-page":"5088","DOI":"10.1073\/pnas.74.11.5088","article-title":"Phylogenetic structure of the prokaryotic domain: the primary kingdoms","volume":"74","author":"Woese","year":"1977","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021032400074182200_ref45","doi-asserted-by":"crossref","first-page":"e00069","DOI":"10.1128\/mSystems.00069-18","article-title":"Evaluating the information content of shallow shotgun metagenomics","volume":"3","author":"Hillmann","year":"2018","journal-title":"MSystems"},{"key":"2021032400074182200_ref46","doi-asserted-by":"crossref","first-page":"325","DOI":"10.2307\/1942268","article-title":"An ordination of upland forest communities of southern Wisconsin, ecological monographs","volume":"27","author":"BRAy","year":"1957","journal-title":"J Ecol Monogr"},{"key":"2021032400074182200_ref47","volume-title":"Information Theory, Inference and Learning Algorithms","author":"MacKay","year":"2003"},{"key":"2021032400074182200_ref48","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.2517-6161.1953.tb00135.x","article-title":"New light on the correlation coefficient and its transforms","volume":"15","author":"Hotelling","year":"1953","journal-title":"J R Stat Soc Ser B"},{"key":"2021032400074182200_ref49","doi-asserted-by":"crossref","DOI":"10.4324\/9780203726631","volume-title":"Research Design and Statistical Analysis","author":"Myers","year":"2013"},{"key":"2021032400074182200_ref50","doi-asserted-by":"crossref","first-page":"26112","DOI":"10.1103\/PhysRevE.67.026112","article-title":"Hierarchical organization in complex networks","volume":"67","author":"Ravasz","year":"2003","journal-title":"Phys Rev E"},{"key":"2021032400074182200_ref51","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1126\/science.1073374","article-title":"Hierarchical organization of modularity in metabolic networks","volume":"297","author":"Ravasz","year":"2002","journal-title":"Science (80-)"},{"key":"2021032400074182200_ref52","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1101\/gr.217202","article-title":"Engineering a reduced Escherichia coli genome","volume":"12","author":"Kolisnychenko","year":"2002","journal-title":"Genome Res"},{"key":"2021032400074182200_ref53","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/16483","article-title":"Robustness in bacterial chemotaxis","volume":"397","author":"Alon","year":"1999","journal-title":"Nature"},{"key":"2021032400074182200_ref54","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/pmic.200300636","article-title":"Functional and topological characterization of protein interaction networks","volume":"4","author":"Yook","year":"2004","journal-title":"Proteomics"},{"key":"2021032400074182200_ref55","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1126\/science.1090289","article-title":"A protein interaction map of Drosophila melanogaster","volume":"302","author":"Giot","year":"2003","journal-title":"Science (80-)."},{"key":"2021032400074182200_ref56","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/nrmicro2832","article-title":"Microbial interactions: from networks to models","volume":"10","author":"Faust","year":"2012","journal-title":"Nat Rev Microbiol"},{"key":"2021032400074182200_ref57","doi-asserted-by":"crossref","first-page":"C47","DOI":"10.1038\/35011540","article-title":"From molecular to modular cell biology","volume":"402","author":"Hartwell","year":"1999","journal-title":"Nature"},{"key":"2021032400074182200_ref58","volume-title":"Introduction to Complex Networks: Models Structures and Dynamics","author":"Chen","year":"2012"},{"key":"2021032400074182200_ref59","first-page":"1415","article-title":"Bioinformatics tools for quantitative and functional metagenome and metatranscriptome data analysis in microbes","volume":"19","author":"Niu","year":"2017","journal-title":"Brief Bioinform"},{"key":"2021032400074182200_ref60","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1073\/pnas.1116053109","article-title":"Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease","volume":"109","author":"Greenblum","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021032400074182200_ref61","doi-asserted-by":"crossref","first-page":"12804","DOI":"10.1073\/pnas.1300926110","article-title":"Metabolic modeling of species interaction in the human microbiome elucidates community-level assembly rules","volume":"110","author":"Levy","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021032400074182200_ref62","doi-asserted-by":"crossref","first-page":"15393","DOI":"10.1038\/ncomms15393","article-title":"Global metabolic interaction network of the human gut microbiota for context-specific community-scale analysis","volume":"8","author":"Sung","year":"2017","journal-title":"Nat Commun"},{"key":"2021032400074182200_ref63","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/s41564-017-0084-4","article-title":"Metatranscriptome of human faecal microbial communities in a cohort of adult men","volume":"3","author":"Abu-Ali","year":"2018","journal-title":"Nat Microbiol"},{"key":"2021032400074182200_ref64","doi-asserted-by":"crossref","first-page":"15007","DOI":"10.1038\/npjbiofilms.2015.7","article-title":"Comparative integrated omics: identification of key functionalities in microbial community-wide metabolic networks","volume":"1","author":"Roume","year":"2015","journal-title":"Biofilms and Microbiomes"},{"key":"2021032400074182200_ref65","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/ismej.2011.85","article-title":"The oral metagenome in health and disease","volume":"6","author":"Belda-Ferre","year":"2012","journal-title":"ISME J"},{"key":"2021032400074182200_ref66","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.3389\/fmicb.2015.01027","article-title":"Next-generation sequencing (NGS) for assessment of microbial water quality: current progress, challenges, and future opportunities","volume":"6","author":"Tan","year":"2015","journal-title":"Front Microbiol"},{"key":"2021032400074182200_ref67","doi-asserted-by":"crossref","first-page":"e1002606","DOI":"10.1371\/journal.pcbi.1002606","article-title":"Microbial co-occurrence relationships in the human microbiome","volume":"8","author":"Faust","year":"2012","journal-title":"PLoS Comput Biol"},{"key":"2021032400074182200_ref68","doi-asserted-by":"crossref","first-page":"P11","DOI":"10.1186\/1465-6906-12-S1-P11","article-title":"Accurate and fast estimation of taxonomic profiles from metagenomic shotgun sequences","volume":"12","author":"Liu","year":"2011","journal-title":"Genome Biol"},{"key":"2021032400074182200_ref69","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat Biotechnol"},{"key":"2021032400074182200_ref70","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/nmeth.2604","article-title":"UPARSE: highly accurate OTU sequences from microbial amplicon reads","volume":"10","author":"Edgar","year":"2013","journal-title":"Nat Methods"},{"key":"2021032400074182200_ref71","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1038\/nmeth.3589","article-title":"MetaPhlAn2 for enhanced metagenomic taxonomic profiling","volume":"12","author":"Truong","year":"2015","journal-title":"Nat Methods"},{"key":"2021032400074182200_ref72","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1038\/s41467-019-08844-4","article-title":"Microbial abundance, activity and population genomic profiling with mOTUs2","volume":"10","author":"Milanese","year":"2019","journal-title":"Nat Commun"},{"key":"2021032400074182200_ref73","first-page":"1","article-title":"MicroPro: using metagenomic unmapped reads to provide insights into human microbiota and disease associations","volume":"20","author":"Zhu","year":"2019","journal-title":"Genome Biol"},{"key":"2021032400074182200_ref74","doi-asserted-by":"crossref","DOI":"10.1093\/bioinformatics\/btz414","article-title":"MetaQUBIC: a computational pipeline for gene-level functional profiling of metagenome and metatranscriptome","author":"Ma","year":"2019","journal-title":"Bioinformatics"},{"key":"2021032400074182200_ref75","doi-asserted-by":"crossref","first-page":"26447","DOI":"10.1038\/srep26447","article-title":"MetaTrans: an open-source pipeline for metatranscriptomics","volume":"6","author":"Martinez","year":"2016","journal-title":"Sci Rep"},{"key":"2021032400074182200_ref76","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1186\/s12859-016-1270-8","article-title":"SAMSA: a comprehensive metatranscriptome analysis pipeline","volume":"17","author":"Westreich","year":"2016","journal-title":"BMC Bioinformatics"},{"key":"2021032400074182200_ref77","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1186\/1471-2105-9-386","article-title":"The metagenomics RAST server\u2014a public resource for the automatic phylogenetic and functional analysis of metagenomes","volume":"9","author":"Meyer","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2021032400074182200_ref78","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/s41592-018-0176-y","article-title":"Species-level functional profiling of metagenomes and metatranscriptomes","volume":"15","author":"Franzosa","year":"2018","journal-title":"Nat Methods"},{"key":"2021032400074182200_ref79","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1021\/acs.jproteome.7b00640","article-title":"IdentiPy: an extensible search engine for protein identification in shotgun proteomics","volume":"17","author":"Levitsky","year":"2018","journal-title":"J Proteome Res"},{"key":"2021032400074182200_ref80","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1002\/pmic.200900375","article-title":"A guided tour of the trans-proteomic pipeline","volume":"10","author":"Deutsch","year":"2010","journal-title":"Proteomics"},{"key":"2021032400074182200_ref81","doi-asserted-by":"crossref","first-page":"W276","DOI":"10.1093\/nar\/gkx411","article-title":"compleXView: a server for the interpretation of protein abundance and connectivity information to identify protein complexes","volume":"45","author":"Solis-Mezarino","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2021032400074182200_ref82","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.1002\/rcm.5245","article-title":"Pathos: a web facility that uses metabolic maps to display experimental changes in metabolites identified by mass spectrometry","volume":"25","author":"Leader","year":"2011","journal-title":"Rapid Commun Mass Spectrom"},{"key":"2021032400074182200_ref83","doi-asserted-by":"crossref","first-page":"W486","DOI":"10.1093\/nar\/gky310","article-title":"MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis","volume":"46","author":"Chong","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2021032400074182200_ref84","first-page":"443903","article-title":"Netome: a computational framework for metabolite profiling and omics network analysis","author":"Rahnavard","year":"2018","journal-title":"BioRxiv"},{"key":"2021032400074182200_ref85","doi-asserted-by":"crossref","first-page":"e1002687","DOI":"10.1371\/journal.pcbi.1002687","article-title":"Inferring correlation networks from genomic survey data","volume":"8","author":"Friedman","year":"2012","journal-title":"PLoS Comput Biol"},{"key":"2021032400074182200_ref86","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1093\/bioinformatics\/btv364","article-title":"Investigating microbial co-occurrence patterns based on metagenomic compositional data","volume":"31","author":"Ban","year":"2015","journal-title":"Bioinformatics"},{"key":"2021032400074182200_ref87","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1093\/bioinformatics\/btv349","article-title":"CCLasso: correlation inference for compositional data through Lasso","volume":"31","author":"Fang","year":"2015","journal-title":"Bioinformatics"},{"key":"2021032400074182200_ref88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12859-019-2915-1","article-title":"Difficulty in inferring microbial community structure based on co-occurrence network approaches","volume":"20","author":"Hirano","year":"2019","journal-title":"BMC Bioinformatics"},{"key":"2021032400074182200_ref89","doi-asserted-by":"crossref","first-page":"e47711","DOI":"10.1371\/journal.pone.0047711","article-title":"Associations between pathogens in the upper respiratory tract of young children: interplay between viruses and bacteria","volume":"7","author":"Bergh","year":"2012","journal-title":"PLoS One"},{"key":"2021032400074182200_ref90","first-page":"841","article-title":"Preventing over-fitting during model selection via Bayesian regularisation of the hyper-parameters","volume":"8","author":"Cawley","year":"2007","journal-title":"J Mach Learn Res"},{"key":"2021032400074182200_ref91","first-page":"352","article-title":"Stopped training and other remedies for overfitting","author":"Sarle","year":"1996","journal-title":"Comput Sci Stat"},{"key":"2021032400074182200_ref92","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3389\/fmicb.2014.00219","article-title":"Deciphering microbial interactions and detecting keystone species with co-occurrence networks","volume":"5","author":"Berry","year":"2014","journal-title":"Front Microbiol"},{"key":"2021032400074182200_ref93","first-page":"609","article-title":"Challenges in the quest for keystones","volume":"46","author":"Daily","year":"1996","journal-title":"Sciences (New York)"},{"key":"2021032400074182200_ref94","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1111\/mec.12571","article-title":"Diffuse symbioses: roles of plant\u2013plant, plant\u2013microbe and microbe\u2013microbe interactions in structuring the soil microbiome","volume":"23","author":"Bakker","year":"2014","journal-title":"Mol Ecol"},{"key":"2021032400074182200_ref95","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41591-018-0308-z","article-title":"Microbial network disturbances in relapsing refractory Crohn\u2019s disease","volume":"25","author":"Yilmaz","year":"2019","journal-title":"Nat Med"},{"key":"2021032400074182200_ref96","doi-asserted-by":"crossref","first-page":"e0225382","DOI":"10.1371\/journal.pone.0225382","article-title":"Biomarker discovery in inflammatory bowel diseases using network-based feature selection","volume":"14","author":"Abbas","year":"2019","journal-title":"PLoS One"},{"key":"2021032400074182200_ref97","first-page":"15","article-title":"Detecting interaction networks in the human microbiome with conditional granger causality","author":"Mainali","year":"2019","journal-title":"PLoS Comput Biol"},{"key":"2021032400074182200_ref98","doi-asserted-by":"crossref","first-page":"e00209-17","DOI":"10.1128\/mSystems.00209-17","article-title":"From network analysis to functional metabolic modeling of the human gut microbiota","volume":"3","author":"Bauer","year":"2018","journal-title":"MSystems"},{"key":"2021032400074182200_ref99","first-page":"9600","article-title":"The players may change but the game remains: network analyses of ruminal microbiomes suggest taxonomic differences mask functional similarity","volume":"43","author":"Taxis","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2021032400074182200_ref100","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature11450","article-title":"A metagenome-wide association study of gut microbiota in type 2 diabetes","volume":"490","author":"Qin","year":"2012","journal-title":"Nature"},{"key":"2021032400074182200_ref101","doi-asserted-by":"crossref","first-page":"D457","DOI":"10.1093\/nar\/gkv1070","article-title":"KEGG as a reference resource for gene and protein annotation","volume":"44","author":"Kanehisa","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2021032400074182200_ref102","doi-asserted-by":"crossref","first-page":"D633","DOI":"10.1093\/nar\/gkx935","article-title":"The MetaCyc database of metabolic pathways and enzymes","volume":"46","author":"Caspi","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2021032400074182200_ref103","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.3389\/fmicb.2017.01606","article-title":"Analysis of microbial functions in the rhizosphere using a metabolic-network based framework for metagenomics interpretation","volume":"8","author":"Ofaim","year":"2017","journal-title":"Front Microbiol"},{"key":"2021032400074182200_ref104","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/nature07540","article-title":"A core gut microbiome in obese and lean twins","volume":"457","author":"Turnbaugh","year":"2009","journal-title":"Nature"},{"key":"2021032400074182200_ref105","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41467-017-00900-1","article-title":"The gut microbiome in atherosclerotic cardiovascular disease","volume":"8","author":"Jie","year":"2017","journal-title":"Nat Commun"},{"key":"2021032400074182200_ref106","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1111\/1751-7915.13284","article-title":"No wisdom in the crowd: genome annotation in the era of big data\u2013current status and future prospects","volume":"11","author":"Danchin","year":"2018","journal-title":"J Microbial Biotechnol"},{"key":"2021032400074182200_ref107","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.tim.2005.12.006","article-title":"Metaproteomics: studying functional gene expression in microbial ecosystems","volume":"14","author":"Wilmes","year":"2006","journal-title":"Trends Microbiol"},{"key":"2021032400074182200_ref108","doi-asserted-by":"crossref","first-page":"e00019-17","DOI":"10.1128\/mSystems.00019-17","article-title":"The protein interactome of Streptococcus pneumoniae and bacterial meta-interactomes improve function predictions","volume":"2","author":"Wuchty","year":"2017","journal-title":"MSystems"},{"key":"2021032400074182200_ref109","doi-asserted-by":"crossref","first-page":"4203","DOI":"10.1021\/ac303053e","article-title":"Metaproteomics: harnessing the power of high performance mass spectrometry to identify the suite of proteins that control metabolic activities in microbial communities","volume":"85","author":"Hettich","year":"2013","journal-title":"Anal Chem"},{"key":"2021032400074182200_ref110","doi-asserted-by":"crossref","first-page":"e1006474","DOI":"10.1371\/journal.pcbi.1006474","article-title":"Genomic data integration systematically biases interactome mapping","volume":"14","author":"Skinnider","year":"2018","journal-title":"PLoS Comput Biol"},{"key":"2021032400074182200_ref111","doi-asserted-by":"crossref","first-page":"15519","DOI":"10.1038\/srep15519","article-title":"Genome-wide protein-protein interactions and protein function exploration in cyanobacteria","volume":"5","author":"Lv","year":"2015","journal-title":"Sci Rep"},{"key":"2021032400074182200_ref112","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/978-94-010-0448-0_11","article-title":"Metabolomics\u2014the link between genotypes and phenotypes","volume":"48","author":"Fiehn","year":"2002","journal-title":"Funct Genom"},{"key":"2021032400074182200_ref113","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nrm3314","article-title":"Innovation: metabolomics: the apogee of the omics trilogy","volume":"13","author":"Patti","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2021032400074182200_ref114","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3390\/microorganisms7010019","article-title":"Microbial fermentation of dietary protein: an important factor in diet\u2013microbe\u2013host interaction","volume":"7","author":"Diether","year":"2019","journal-title":"Microorganisms"},{"key":"2021032400074182200_ref115","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3390\/metabo7040062","article-title":"Computational approaches for integrative analysis of the metabolome and microbiome","volume":"7","author":"Chong","year":"2017","journal-title":"Metabolites"},{"key":"2021032400074182200_ref116","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1038\/s41467-019-10927-1","article-title":"Predictive metabolomic profiling of microbial communities using amplicon or metagenomic sequences","volume":"10","author":"Mallick","year":"2019","journal-title":"Nat Commun"},{"key":"2021032400074182200_ref117","doi-asserted-by":"crossref","first-page":"14482","DOI":"10.1073\/pnas.0806162105","article-title":"Large-scale reconstruction and phylogenetic analysis of metabolic environments","volume":"105","author":"Borenstein","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021032400074182200_ref118","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/B978-0-12-407863-5.00011-3","article-title":"Sequential isolation of metabolites, RNA, DNA, and proteins from the same unique sample","volume":"531","author":"Roume","year":"2013","journal-title":"Methods Enzymol"},{"key":"2021032400074182200_ref119","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.coisb.2019.03.007","article-title":"Biological insights through omics data integration","volume":"15","author":"Noor","year":"2019","journal-title":"Curr Opin Syst Biol"},{"key":"2021032400074182200_ref120","doi-asserted-by":"crossref","first-page":"W505","DOI":"10.1093\/nar\/gks445","article-title":"SteinerNet: a web server for integrating \u2018omic\u2019 data to discover hidden components of response pathways","volume":"40","author":"Tuncbag","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2021032400074182200_ref121","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nmeth.2810","article-title":"Similarity network fusion for aggregating data types on a genomic scale","volume":"11","author":"Wang","year":"2014","journal-title":"Nat Methods"},{"key":"2021032400074182200_ref122","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1093\/biostatistics\/kxu001","article-title":"Variable selection for generalized canonical correlation analysis","volume":"15","author":"Tenenhaus","year":"2014","journal-title":"Biostatistics"},{"key":"2021032400074182200_ref123","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1093\/bioinformatics\/bty1054","article-title":"DIABLO: An integrative approach for identifying key molecular drivers from multi-omics assays","volume":"35","author":"Singh","year":"2019","journal-title":"Bioinformatics"},{"key":"2021032400074182200_ref124","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s13238-018-0544-5","article-title":"Single-cell metagenomics: challenges and applications","volume":"9","author":"Xu","year":"2018","journal-title":"Protein Cell"},{"key":"2021032400074182200_ref125","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.gpb.2013.01.004","article-title":"Global genomic arrangement of bacterial genes is closely tied with the total transcriptional efficiency","volume":"11","author":"Ma","year":"2013","journal-title":"Genomics Proteomics Bioinformatics"},{"key":"2021032400074182200_ref126","doi-asserted-by":"crossref","first-page":"6310","DOI":"10.1073\/pnas.0911237107","article-title":"Genomic arrangement of bacterial operons is constrained by biological pathways encoded in the genome","volume":"107","author":"Yin","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021032400074182200_ref127","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13073-017-0448-7","article-title":"Dissecting the human microbiome with single-cell genomics","volume":"9","author":"Tolonen","year":"2017","journal-title":"Genome Med"},{"key":"2021032400074182200_ref128","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1038\/nmeth.4469","article-title":"The trajectory of microbial single-cell sequencing","volume":"14","author":"Woyke","year":"2017","journal-title":"Nat Methods"},{"key":"2021032400074182200_ref129","first-page":"426106","article-title":"Visualizing metabolic network dynamics through time-series metabolomics data","author":"Buchweitz","year":"2018","journal-title":"bioRxiv"},{"key":"2021032400074182200_ref130","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/BF01386390","article-title":"A note on two problems in connexion with graphs","volume":"1","author":"Dijkstra","year":"1959","journal-title":"Numer Math"},{"key":"2021032400074182200_ref131","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1093\/bioinformatics\/btv161","article-title":"MAGNA++: maximizing accuracy in global network alignment via both node and edge conservation","volume":"31","author":"Vijayan","year":"2015","journal-title":"Bioinformatics"},{"key":"2021032400074182200_ref132","doi-asserted-by":"crossref","first-page":"e1005466","DOI":"10.1371\/journal.pcbi.1005466","article-title":"A review of active learning approaches to experimental design for uncovering biological networks","volume":"13","author":"Sverchkov","year":"2017","journal-title":"PLoS Comput Biol"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/22\/2\/1639\/36654613\/bbaa005.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/bib\/article-pdf\/22\/2\/1639\/36654613\/bbaa005.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T22:55:28Z","timestamp":1722293728000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/22\/2\/1639\/5734243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,11]]},"references-count":132,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2,11]]},"published-print":{"date-parts":[[2021,3,22]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbaa005","relation":{},"ISSN":["1477-4054"],"issn-type":[{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,3]]},"published":{"date-parts":[[2020,2,11]]}}}