CAS Key Laboratory of Genome Sciences & Information
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1. Introduction

After the institute actively participated in the International Human Genome Project (HGP), the institute also led the Chinese Super-hybrid Rice Genome Project, the chicken and silkworm genome projects. Approved by CAS, the institute founded the CAS Key Laboratory of Genome Sciences and Information on November 2006 under the background of propulsion stage of CAS Knowledge Innovation Project propulsion and rapid development of genome science and bioinformatics. Since establishment in November 2006, it has always been for the national strategic needs and world scientific frontier. With the core task of genome sciences and information studies and purpose of establishing genomics and bioinformatics organic research system, the lab focuses on major basic scientific problems in order to promote research and application of genomics in China, such as human health, agricultural development, environment and other major life science and technology issues.

2. Research location

Based on the frontier fields of genomics and information technology, our library focuses on the national strategic demands of population health and biosecurity. We will develop new theories about genome structure, mutation, function and evolution, and we will also build new methods and technologies about the massive biological data acquisition, integration and mining. We aim to enhance the cross-fertilization of genomics and other disciplines and to promote integration and forward-looking research by data-driven genomic problem. Our major goal is to address key life sciences and technology issues such as public safety, biosecurity and data security.

3. Research direction

(1) New mechanism and theory about epigenetic regulation of complex traits.

We aim to reveal the evolution of epigenetic information and its role in the evolution of species, to elucidate how epigenetic information including DNA modification, histone modification, RNA modification guide the reproductive development, cell differentiation and organ formation of animals, and to analyze the molecular mechanism of establishment and maintenance epigenetic information map.

(2) Research on genome structure and plasticity.

Focusing on the key issues of assembling large-scale complex genomic sequences, we will develop new strategies and methods to address the high heterozygous or polyploidy problem. By developing new experimental and computational techniques, we will analyze the dynamic characteristics of genome three-dimensional high-level structures. From multidimensional omics perspective, we will reveal the genetic and epigenetic polymorphism and complexity and the decision mechanism of environmental factors on phenotypic plasticity.

(3) Genomics frontier crossover research and its application.

We will develop new interdisciplinary methods which integrate genomics, mathematics, computer science, medicine and other science. We will also build standardized technical methods which analyze the correlation between omics data and clinical phenotype systematically and quickly. By these new methods, we wish to form the industry standard of the analysis and application of precise medical data. To provide the precise technical support for the public safety, biosecurity and data security, we will build the Chinese population biology characteristics knowledge database by analyze the characteristics of genotype polymorphism, age, facial phenotype, body characteristics and population origin. In addition, we also develop the new technology and software to detect the trace nucleic acid quickly and the efficient method to store and process DNA data.

4. Organization

Director: HU Songnian, Ph.D.
Deputy Director: LIU Jiang, Ph.D.

Academic committee

Director: HE Lin, Ph.D. (Academician, CAS)
Deputy Director: HAN Bin, Ph.D. (Academician, CAS)

CHI Xuebin, Computer Network Information Center, CAS
GONG Fuzhou, Academy of Mathematics and Systems Sciences, CAS
HANG Haiying, Institute of Biophysics, CAS
HU Songnian, Beijing Institute of Genomics, CAS
HUANG Luqi, China Academy of Chinese Medical Sciences (Academician, CAS)
LI Yixue, Shanghai Institutes for Biological Sciences, CAS
QI Yijun, National Institute of Biological Sciences, Beijing
SUN Xiaowen, Chinese Academy of Fishery Sciences
TONG Yigang, Academy of Military Medical Sciences
WANG Guoyin, Chongqing University of Posts and Telecommunications
XUE Yongbiao, Beijing Institute of Genomics, CAS
YU Jun, Beijing Institute of Genomics, CAS
Ye Jian, Institute of Forensic Science Ministry of Public Security

Consultative committee

Director: CHEN Runsheng, Bioinformatics Institute of Biophyscis, CAS
CHEN Shouyi, Institute of Genetics and Developmental Biology, CAS
CHENG Linzhao, Johns Hopkins School of Medicine
GU Xun, Iowa State University
LI Lingheng, Stowers Institute for Medical Research
MENG Anming, Institute of Zoology, CAS
ZHU Lihuang, Institute of Genetics and Developmental Biology, CAS

5. Annual research progress

(1) 3D Chromatin Structures of Mature Gametes and Structural Reprogramming during Mammalian Embryogenesis

High-order chromatin structure plays important roles in gene expression regulation. Knowledge of the dynamics of 3D chromatin structures during mammalian embryo development remains limited. We report the 3D chromatin architecture of mouse gametes and early embryos using an optimized Hi-C method with low-cell samples. We find that mature oocytes at the metaphase II stage do not have topologically associated domains (TADs). In sperm, extra-longrange interactions (>4 Mb) and interchromosomal interactions occur frequently. The high-order structures of both the paternal and maternal genomes in zygotes and two-cell embryos are obscure but are gradually re-established through development. The establishment of the TAD structure requires DNA replication but not zygotic genome activation. Furthermore, unmethylated CpGs are enriched in A compartment, and methylation levels are decreased to a greater extent in A compartment than in B compartment in embryos. In summary, the global reprogramming of chromatin architecture occurs during early mammalian development.

(2) Multi-Omics Data Integration of Rice Endosperm

Rice seeds accumulate a large amount of starch during maturation and provide the main energy for seed germination and seedling growth. On the other hand, starch is also a main source of energy storage for the human, and the accumulation of starch have influences on physical characteristics of rice such as size, weight and the rice yield. Songnian Hu’s group has collected rice cultivars with different starch content from different areas and designed a new method of measuring starch content in order to obtain the relative starch content of 61 rice cultivars. By employing NGS technology, a project of 30 rice cultivars with multi-omics (transcriptome, methylatome and re-sequencing) was conducted. A total of 1233 positive-correlated genes with starch content and 47 negatives were obtained by a new analysis method named CDEGA (Co-Differential-Expression-Genes-Analysis). Then, we constructed a basic regulatory module of rice starch from the perspective of multi-lineage SNP analysis, pre-transcriptional regulation (methylation level) and post-transcriptional regulation (miRNA and LncRNA levels).

(3) Transcriptome Analysis of Monozygotic Twin Brothers with Childhood Primary Myelofibrosis

Primary myelofibrosis (PMF) is a chronic myeloproliferative disorder in human bone marrow. Over 50% of patients with myelofibrosis have mutations in JAK2, MPL, or CALR. However, these mutations are rarely detected in children, suggesting a difference in the pathogenesis of childhood PMF. Here we investigated the response to drug treatment of a monozygotic twin pair with typical childhood PMF. The twin exhibited different clinical outcomes despite following the same treatment regimen. The transcriptomic profiles of patient samples after drug treatment were significantly different between the twin pair, which is consistent with the observation that the drug treatment was effective only in the younger brother. Bioinformatics analysis of the drug-responsive genes showed that the JAK-STAT pathway was activated in the cured younger brother, which is opposite to the pathway inhibition observed in adult PMF cases following treatment. Moreover, apoptosis and cell cycle processes were both significantly influenced by drug treatment in the sample of younger brother, implying their potential association with the pathogenesis of childhood PMF. The current study reported at transcriptomic level the different responses of monozygotic twin brothers with childhood PMF to the same androgen/prednisone treatment regimen providing new insights into the potential pathogenesis of childhood PMF for clinical applications.

(4) Characteristic Arrangement of Nucleosomes is Predictive of Chromatin Interactions at Kilobase Resolution

High-throughput chromosome conformation capture (3C) technologies, such as Hi-C, have made it possible to survey 3D genome structure. However, obtaining 3D profiles at kilobase resolution at low cost remains a major challenge. Therefore, we herein present an algorithm for precise identification of chromatin interaction sites at kilobase resolution from MNase-seq data, termed chromatin interaction site detector (CISD), and a CISD-based chromatin loop predictor (CISD loop) that predicts chromatin–chromatin interactions (CCIs) from low-resolution Hi-C data. We show that the predictions of CISD and CISD loop overlap closely with chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) anchors and loops, respectively. The validity of CISD/CISD loop was further supported by a 3C assay at about 5 kb resolution. Finally, we demonstrate that only modest amounts of MNase-seq and Hi-C data are sufficient to achieve ultrahigh resolution CCI maps. Our results suggest that CCIs may result in characteristic nucleosomes arrangement patterns flanking the interaction sites, and our algorithms may facilitate precise and systematic investigations of CCIs on a larger scale than hitherto have been possible.

(5) RNA Profiling Analysis of the Serum Exosomes Derived from Patients with Active and Latent Mycobacterium Tuberculosis Infection

Tuberculosis (TB) has exceeded HIV as the most lethal infectious disease globally for two consecutive years. Moreover, one third of the world’s population is estimated to have latent tuberculosis infection (LTBI). This is mainly because of difficulties associated with diagnosis and treatment for both TB and LTBI patients. Exosomes provide a promising research tool for TB diagnosis and treatment because they are released from various cells containing valuable biochemical information related to disease. In this study, we performed RNA-sequencing analysis on exosomes derived from clinical specimens of healthy controls (HC), active tuberculosis (ATB), and LTBI patients. Our results revealed the distinct gene expression profiles of the exosomes from LTBI and ATB patients. Here we identified many distinct up-regulated and down-regulated differentially expressed genes (DEGs) in LTBI and ATB samples, and further screened the top-20 DEGs which might provide a potential panel for differentiation of HC, LTBI, and ATB. In addition, we classified the DEGs into six expression patterns, screened the top-20 genes in each pattern, and mainly focused on those highly expressed in LTBI and ATB. Our findings indicate the selective packaging of RNA cargoes into exosomes under different stages of Mtb infection, while facilitating the development of potential targets for the diagnosis, prevention and treatment of tuberculosis.

(6) Increased Oxidative Stress Reshapes Airway Microbiomes of Cystic Fibrosis Patients

The lethal chronic infections in Cystic fibrosis (CF) airway is predisposed by colonization of specific CF-philic pathogens (CF pathogens), while the molecular mechanisms of which are not fully understood.We perform a meta-analysis of airway microbiome of CF patients. Metabolic network is reconstructed based on genome information of component species. Moreover, we quantitatively evaluate the anti-oxidative stress (anti-OS) capacity of each species after constructing a comprehensive database of anti-OS genes. CF microbiomes engage much more redox-related activities than controls. Quantitative evaluation of anti-OS capacity confirms the conservation of anti-OS response within genus, and indicates significant higher values of CF pathogens than commensals and other typical respiratory pathogens. The anti-OS capacity of a species correlates with its relative fitness between CF and normal airways. Moreover, the total anti-OS capacities of a microbiome are higher in CF than normal, and increases along disease progression, especially after episodes of acute exacerbation and antibiotic treatment. The increased oxidative stress in CF airways reshapes the microbiomes to a more resistant status and selects for resistant CF pathogens but not sensitive commensals, which favors the pre-infection colonization of CF pathogens for their higher anti-OS capacities.

6. Awards and Honors

LIU Jiang The National Key Talent Project
YU Jun, CAS Distinguished Research Fellow
YU Jun, Director, committee of precision medicine and cancer rehabilitation, CARTTP
HU Songnian, Associate Director, committee of precision medicine and cancer rehabilitation, CARTTP
FANG Xiangdong, Council member of Chinese Union of Translational Medicine (CUTM)
FANG Xiangdong, member of Clinical Genetics Specialist Committee of National Health and Family Planning Commission of the PRC
FANG Xiangdong, member of People’s Medical Publishing House Periodical Management Committee
FANG Xiangdong, member of health and medical big data government decision and standardization Specialized Committee, Chinese Health Information Association
FANG Xiangdong, member of Biological Diagnostic Technology committee, China Medicinal Biotech Association
LUO Yingfeng was selected as the members of 2017 Youth Innovation Promotion Association of CAS.