Challenges and opportunities in investigation of human gut metagenomics
Human gut microbiota is an important factor which can reflect or affect the state of human health. Many studies already show that the biodiversity is closely related to many chronic non-communicable diseases, such as obesity, diabetes, cancer etc. However, human gut microbiome is one of the most complicated microbial communities, which contains over 1000 known species and nine million of functional genes. It is estimated that there are still a large number of gut microbes remaining unrevealed due to the difficulty of culture, especially for those species with rare or low abundance. The properties and functions of these low abundance microbial in human guts are still a black box. The present metagenomic sequencing technologies have some limitations in detection of the microbial with the abundance less than 0.1%. The technological difficulties exist in both library fabrication and bioinformatic process.
Several efforts have been published to target the problems, including eigengenome partitioning, mini-metagenome, synthetic long-read sequencing, etc.. Here we will introduce a new strategy to solve the problem. Firstly, we found the differences of the sequence similarity between the genes of different species (gene uniqueness) by analyzing the genomes of the known microbiota in the human guts. Furthermore, we divided the microbiota into more than 100 sub-mcirobiota with limited cell numbers in order to reduce the complexity. We can obtain the more readers from low abundance microbial and cluster the different short de novo assembled contigs into high quality long contigs based on gene uniqueness. It is indicated that a number of low abundance species have been detected and a lot of novel genes have been found with this method. The method would help us to discover more unknown species and understand influences of the low abundance microbial in human guts.
Zuhong Lu received the BS and MS degrees in electronics engineering and Ph.D degree in bioelectronics from the Southeast University at Nanjing, China in 1982,1984 and 1988,respectively. He currently is the Cheung Kong Professor at School of Biological Science and Medical Engineering of Southeast University, Director of State Key Laboratory for Bioelectronics. He was previously Chair Professor of Department of Biomedical engineering，College of Engineering, Peking University. He is currently Chair of the Society of Biomedical Electronics, Chinese Electronics Institute，and Chair of Branch of Health Engineering, Chinese Society of Biomedical Engineering. His research field covers molecular devices, biosensors, microarray technology, microfluidics, high throughput DNA sequencing, bioinformatics, health engineering, etc. He has published more than 400 peer-reviewed papers, and obtained more than 30 national patents.