Group leader
Dr. LI is a professor and principal investigator at Beijing Institute of Genomics (BIG), Chinese Academy of Sciences (CAS). Dr. LI received the B.S. and M.S. degrees in Biology from Northwest A & F University, Shannxi, China in 2006. He received a Ph.D. in Bioinformatics/Genetics from Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany in July 2012 (advisor: Dr. Mark Stoneking), and did postdoctoral research in the same lab until Oct 2013. He held a position as Senior Scientist/Bioinformatics Group leader at Fondation Merieux, Lyon, France before joining BIG. Dr. LI's expertise is bioinformatics, metagenomics, and molecular evolution.
Introduction
LI lab is currently focusing on two topics:.
1. lung microbiome
The lung is relatively sterile compared to the gut; however, the importance of the lung microbiome in health has been well recognized. Alternation of the lung microbiome has been associated with clinical and inflammatory features of several respiratory tract diseases, thus making it a potential target for novel diagnostic and therapeutic approaches. However, the baseline of the lung microbiome is still largely unclear, especially for non-Caucasian populations. The group is trying to answer the following questions:
What is the core microbiome in the lung?
How the lung microbiome alter during infection?
How microbiome differs between lower respiratory tract and upper respiratory tract?
How microbiome interacts with the host gene expression?
How the viral genome evolves after infecting human?
2. Mitochondrial DNA
Mitochondrion has its own genomic DNA(mtDNA), that has thousands copies in each cell. Its mutation rate is about 10 times higher than that of nuclear DNA and very few recombinations were observed on mtDNA(maternal inherited), thus making it a frequently-used molecular biomarker in population genetics studies. Meanwhile, mtDNA mutations are known to be associated with several inherited diseases, and these pathogenic mutations as well as other "neutral" mutations are normally in heteroplasmic states (a mixture of wild type and mutant type), which is hard to be detected by ordinary method. With the development of Next-generation Sequencing, it is feasible to identify many low-level heteroplasmies, thus enable us to reexamine the fundamental theory of mtDNA inheritance, including:
Whether paternal leakage exists during mtDNA inheritance?
Whether recombination occurs on mtDNA?
Whether the mtDNA mutation pattern differs between cell line and fresh tissue?
We are collaborating with Max Planck Institute and Genome of the Netherlands consortium on this work.
Selected publications
Human mtDNA genomics and population genetics
1. Li MK, Rothwell R, Vermaat M, Wachsmuth Manja, Schroder R, et al. Genome of the Netherlands Consortium. 2016. Transmission of human mtDNA heteroplasmy in the genome of the Netherlands families: support for a variable-size bottleneck. Genome Research, 10.1101/gr.203216.115
2. Li MK, Schroeder R, Ni SY, Madea B, Stoneking M. 2015. Extensive tissue-related and allele-related mtDNA heteroplasmy suggests positive selection for somatic mutations. PNAS. 112(8):2491-6
3. Wachsmuth M, Huebner A, Li MK, Madea B, Stoneking M. 2016. Age-related and heteroplasmy-related variation in human mtDNA copy number. Plos Genet, 12(3): e1005939
4 The Genome of the Netherlands Consortium. 2014. Whole-genome sequence variation, population structure and demographic history of the Netherlands. Nature Genetics. 46(8):818-25.
5. Malaspinas AS, Lao O, Schroeder H, Rasmussen M, Raghavan M, Moltke I, Campos PF, Santana Sagredo F, Rasmussen S, Gon？alves VF, Albrechtsen A, Allentoft ME, Johnson PLF, Li MK, et al. 2014. Two ancient human genomes reveal Polynesian ancestry among the indigenous Botocudos of Brazil. Current Biology. 24(21):R1035-7
6. Lippold S, Xu HY, Ko A, Li MK, Renaud G, Butthof A, Schroeder R, Stoneking M. 2014. Human paternal and maternal demographic histories: insights from high-resolution Y chromosome and mtDNA sequences. Investigative Genetics. 5:13
7. Rieux A, Eriksson A, Li MK, Sobkowiak B, Weinert LA, Warmuth V, Ruiz-Linares A, Manica A, Balloux F. 2014. Improved calibration of the human mitochondrial clock using ancient genomes. Molecular Biology and Evolution. 31(10):2780-92
8. Giuliani C, Barbieri C, Li MK, et al. 2014. Transmission from centenarians to their offspring of mtDNA heteroplasmy revealed by ultra-deep sequencing. AGING. 6(6):454-67.
9. Ko AMS, Chen CY, Fu Q, Delfin F, Li MK, et al. 2014. Early Austronesians: into and out of Taiwan. American Journal of Human Genetics. 94(3), 426-436
10. Delfin F, Ko A, Li MK, Gunnarsdottir ED, Tabbada K, Salvador JM, Calcacl GC, Sagum MS, Datar FA, Padilla SG, DeUngria MCA, Soneking M. 2013. Complete mtDNA genomes of Filipino ethnolinguistic groups: A melting pot of recent and ancient lineages in the Asia-Pacific region. European Journal of Human Genetics. doi:10.1038
11. Barbieri C, Whitten M, Beyer K, Schreiber H, Li MK, Pakendorf B. 2012. Contrasting Maternal and Paternal Histories in the Linguistic Context of Burkina Faso. Molecular Biology and Evolution, 29 (4): 1213-1223
12. Gunnarsdottir E, Li MK, Bauchet M, Finstermeier K, Stoneking M. 2011. High-throughput sequencing of complete human mtDNA genomes from the Philippines. Genome Research, 21(1):1-11
13. Gunnarsdottir E, Nandineni MR, Li MK, Myles S, Gil D, Pakendorf B, Stoneking M. 2011. Larger mitochondrial DNA than Y-chromosome differences between matrilocal and patrilocal groups from Sumatra. Nature Communication. 2:228
14. Schoenberg A, Theunert C, Li MK, Stoneking M, Nasidze I. 2011. High-throughput sequencing of complete human mtDNA genomes from the Caucasus and West Asia: high diversity and demographic inferences. European Journal of Human Genetics, 19(9):988-94
Low-level mutation detection (Algorithm development)
15. Li MK* and Stoneking M. 2012. A new approach for detecting low-level mutations in next-generation sequence data. Genome Biology, 13:R34.
16. Li MK*, Schroeder R, Ko A, Stoneking M. 2012. Fidelity of capture-enrichment for mtDNA genome sequencing: influence of NUMTs. Nucleic Acid Research, 40:e137.
17. Li MK*, Schoenberg A, Schaefer M, Schroeder R, Nasidze I, Stoneking M*. 2010. Detecting heteroplasmy from high-throughput sequencing of complete human mitochondrial DNA genomes. American Journal of Human Genetics. 87(2):237-49.
Metagenomics
18. Ren L, Yang D, Ren X, Li M, Mu X, Wang Q, Cao J, Hu K, Yan C, Fan H, Li X, Chen Y, Wang R, An F, An S, Luo M, Wang Y, Xiao Y, Xiang Z, Xiao Y, Li L, Huang F, Jin Q, Gao Z, Wang J. 2017. Genotyping of human rhinovirus in adult patients with acute respiratory infections identified predominant infections of genotype A21. Sci Rep. 7: 41601
19. Yan F, Xiao Y, Li M, Zhang H, Zhang R, Zhou H, Shen H, Wang J, Li W, Ren L. 2017, Metagenomic analysis identified human rhinovirus B91 infection in an adult suffered severe pneumonia. Am J Resp Crit Care. 195(11): 1535–1536
20 . Li J, Quinque D, Horz HP, Li MK, Rzhetskaya M, Raff JA, Hayes MG, Stoneking M. 2014. Comparative analysis of the human saliva microbiome from different climate zones: Alaska, Germany, and Africa. BMC Microbiology, 14: 316.
21. Li J, NasidzeI, Quinque D, Li MK, Horz HP, Andre C, Garriga RM, Halbwax M, Fischer A, Stoneking M. 2013. The saliva microbiome of Pan and Homo. BMC Microbilogy 13:204
22. Nasidze I, Li J, Schroeder R, Creasey JL, Li MK, Stoneking M. 2011. High diversity of the saliva microbiome in Batwa Pygmies. Plos One, 6(8):e23352
23. Nasidze I, Quinque D, Li J, Li MK, Tang K, Stoneking M. 2009. Comparative analysis of human saliva microbiome diversity by barcoded pyrosequencing and cloning approaches. Analytical Biochemistry. 391(1):64-8
Molecular evolution
24. Li MK* and Chen SS. 2011. The tendency to recreate ancestral CG dinucleotides in the human genome. BMC Evolutionary Biology. 11:3
25. Li MK, Gu L, Chen SS, Dai JQ, Tao SH. 2008. Evolution of the isochore structure in the scale of chromosome: insight from the mutation bias and fixation bias. Journal of Evolutionary Biology. 21(1):173-82
26. Gong X, Fan S, Bilderbeck A, Li MK, Pang H, Tao S. 2008. Comparative analysis of essential genes and nonessential genes in Escherichia coli K12. Molecular Genetics and Genomics. 279(1):87-94
Awards
Chinese Government Scholarship for Outstanding Self-financed Students Studying Abroad,2011
1000 Talent Yong, 2017
