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18 Dec 2021

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The "encyclopedia" of microbes on earth is here!

The Biomedical Artificial Intelligence Team of the Institute of Science and Technology for Brain-Inspired Intelligence of Fudan University builds a global microbial gene catalog. The results are published in Nature.


Microorganisms are ubiquitous on Earth, hidden on people's skin, gut and soil, rivers, oceans and other environments, forming a complex microbiome community. They symbiotically interact with different hosts in different environments and become an important factor affecting human health and changes in the earth's ecology. Traditional microbiome research is carried out according to different habitats such as human and marine microorganisms, and cannot describe the interrelationship of microbial communities in different habitats from a global perspective.


Luis Pedro Coelho, Prof. Xingming Zhao and Honorary Prof. Peer Bork from the Institute of Science and Technology for Brain-Inspired Intelligence (hereinafter referred to as ISTBI) of Fudan University, cooperated with scientists from Germany, Spain, the United States, the United Kingdom and other countries. Based on the concept of a global microbiome and regarding the different habitats on the earth as a unified system, using artificial intelligence to mine 13,000 publicly available metagenomic samples, they constructed the Global Microbial Gene Catalog (GMGC), the most comprehensive gene catalog so far, which is an important step for global microbial research. The study also found that most genes are habitat-specific, and genes spanning multiple habitats are mainly enriched in antibiotic resistance genes and mobile genetic elements.


In the early morning of December 16, 2021, Beijing time, related research results "Towards the biogeography of prokaryotic genes" were published inNatureas an article. Luis Pedro Coelho is the first author and co-corresponding author of the paper. The research was funded by the European Union’s Horizon 2020 Research and Innovation Programme, the National Key R&D Program of China, the National Natural Science Foundation of China , and the Shanghai Municipal Science and Technology Major Project and other projects.


Build the most comprehensive global microbial gene catalog to date


The gene catalog is of great significance for describing the species composition and functional characteristics of microbial communities. Since the European Molecular Biology Laboratory (EMBL) and BGI-Shenzhen established the first human gut microbial gene catalog in 2010, the emerging microbial gene catalog has provided important clues for the study of human physiology and diseases.  


The Global Microbial Gene Catalog (GMGC, version 1) covers 14 habitats, including gut, oral cavity, skin, ocean, and soil. It collected 13,174 publicly available high-quality metagenomic samples and 84,029 high-quality genomes, resulting in 303 million species-level genes (95% nucleic acid consistency clustering), and the most comprehensive global microbial gene catalog (Figure 1) has been constructed, which will provide important contributions for earth ecological and human health research.



A global microbial gene catalog containing 300 million prokaryotic genes was constructed from 13,000 metagenomic samples and nearly 100,000 bacterial genomes. (a) Construction pipeline of Global microbial gene catalog; (b) Unigenes sharing among different habitats; (c) Unigene cumulative curves; (d) Distribution of the number of unigenes


The GMGC reveals the important relationship between microbial genes and habitat


A unigene may represent genes from multiple habitats. These multi-habitat genes may come from species that live in multiple habitats, or from mobile elements that transfer horizontally between genomes or across habitat boundaries. The study found that most genes are habitat-specific, which is consistent with the characteristics of microorganisms that tend to adapt to the environment; only 5.8% of species-level gene clusters are multi-habitat genes, which are mainly enriched in antibiotic resistance genes and mobile elements.


The sharing of metagenomic species(a), species-level unigene(b), protein function group(c), and protein families(d) between habitats.



The researchers further investigated how frequent unigenes are in metagenomes and found that most unigenes in the GMGCv1 are rare genes with a frequency of less than 0.1%. The prevalence of species-level unigenes follows a power law under the assumption of neutral (or nearly neutral) evolution. In fact, it seems that while there were a lot of variations observed, most of this variation is not adaptation to the environment, but is driven by what is called "neutral evolution": variations that are the result of random chance, and not Darwinian selection.


These findings provide a new perspective to understand the generation of antibiotic resistance and develop antibacterial drugs in the future.


A multi-disciplinary international research team


The Biomedical Artificial Intelligence Group of the ISTBI is an interdisciplinary research group of Fudan University. Since 2018, it has introduced a group of outstanding scholars at home and abroad. The interdisciplinary and international group includes computer science, mathematics, biology, physics, and other backgrounds. In recent years, a series of artificial intelligence algorithms have been developed and successfully applied in biomedical scenarios, such as brain-gut axis, brain development, and brain diseases. These researches have been published in Nature, Science, Cell, Cell Metabolism, IEEE TPAMI, Nature Communications, etc. The team won the first prize of Wu Wenjun AI Science & Technology Award in Journal, 2020.


Li Jin(3rd from the left), academician of Chinese Academy of Sciences and president of Fudan University, awarded Peer Bork an honorary professor certificate. Jianfeng Feng(4th from the right), president of ISTBI, Peer Bork(4th from the left), Xingming Zhao(2nd from the left), and Luis Pedro Coelho(3rd from the right )attended the conference.


The first author of the paper, Luis Pedro Coelho, joined Fudan University full-time in 2018. Prior to that, he focused on the analysis of microbial populations using metagenomics and microscopic image technology. He worked with the Big Data Biology Group, Computational Biology Group and other research groups in ISTBI, a large interdisciplinary team with high internationalization, one-third of whose faculty members are from different countries, and he participated in the construction of the Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Ministry of Education, China. Luis also participated in a number of major research projects about biomedical big data, brain science, and brain-inspired intelligence by big data methods.


As the head of the Biomedical Artificial Intelligence Group of ISTBI, Prof. Xingming Zhao introduced that cutting-edge science is increasingly breaking through the boundaries of disciplines and requires a global perspective. This research has constructed a microbial gene catalog under the global perspective, which plays an important role in understanding the relationship between microbes and human health. For the next step, the team will cooperate with scientific and clinical collaborators to explore the effect of microbes on human health, brain cognition and behavior.


Link: https://www.nature.com/articles/s41586-021-04233-4


Presented by Fudan University Media Center

Source: Institute of Science and Technology for Brain-Inspired Intelligence of Fudan University

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