Biology subjects
Publications and source records attributed to Yang, H..
Amplicon sequencing need to go from using single region to multiple region, one for higher resolution, one for technical replicates. WinnerTakeAlmostAll is an algorithm to calculate a minimum set of references based on the reference-query graph. We showed that this algorithm is superior in resolving species, as well as average out the run effect using technical replicates.
The gut microbiome has been the center of attention for human commensal microbiome studies. The vaginal microbiome is also densely populated with bacteria, viruses and fungi, and the presence of microorganisms beyond the cervix is increasingly reported in non-infectious conditions1-3. Due to the over 90% of human sequences in female reproductive tract samples3,4, metagenomic information has been very limited. 16S rRNA gene amplicon sequencing studies have identified community types in the vaginal microbiota, and observed its dynamic changes due to menstrual cycles and sexual behaviors in small cohorts5,6. Here we perform metagenomic shotgun sequencing on cervical samples from 516 women of reproductive age (more than 10-fold of the Human Microbiome Project (HMP)4), and dissect major factors, especially pregnancy and delivery histories and contraception methods on the microbiome composition. Features of other body sites, such as mood fluctuations and facial speckles could potentially be deduced from the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota in the female reproductive tract and imply disease susceptibilities that may be relieved by behavioural changes.
(1) AimsDue to the ever increasing incidence of T2DM, it is estimated that only half of the 79 million adults with type 2 diabetes (T2DM) will have adequate access to insulin by 2030 if the current levels of access is not improved. It is urgent to identify the important risk factors for T2DM and develop effective strategies to address the problem of T2DM. Our study aimed to evaluate the association between apolipoprotein E (ApoE) genetic polymorphism and type 2 diabetes, and to provide clues for the etiology of T2DM and even molecular marker of targeted therapy for the treatment of T2DM. (2) MethodsCase-control studies of ApoE polymorphism and T2DM, which were included in PubMed, Web of Science, Medline, WanFang, VIP, and CNKI databases, were selected and evaluated according to criteria of inclusion and exclusion. Eligible data were extracted and pooled, and were analyzed and assessed using R soft-ware (version 3.4.3). Random-effect models were used when heterogeneity existed in between-study, and fixed-effect models were applied otherwise. (3) ResultsA total of 59 studies that consisted of 6,872 cases with T2DM and 8,250 controls were selected. Alleles and genotypes of ApoE between cases and controls were compared. For ApoE alleles, we observed the contrast of {varepsilon}4 versus {varepsilon}3 allele yielding a pooled OR of 1.18 (95% CI: 1.09-1.28; P<0.001). For ApoE genotypes, compared with {varepsilon}3/{varepsilon}3 genotype, {varepsilon}2/{varepsilon}2 genotype showed a possible association with T2DM (OR=1.46; 95% CI: 1.11-1.93; P=0.007), {varepsilon}3/{varepsilon}4 genotype had a 1.11-fold risk of developing T2DM (OR=1.11; 95% CI: 1.01-1.22; P=0.039), and {varepsilon}4/{varepsilon}4 genotype had a 1.71-fold risk of developing T2DM (OR=1.71; 95% CI: 1.33-2.19; P<0.001). (4) ConclusionsThere is an association between ApoE polymorphism and T2DM: allele {varepsilon}4 and genotypes ({varepsilon}2/{varepsilon}2, {varepsilon}3/{varepsilon}4, and {varepsilon}4/{varepsilon}4) are associated with the increased risk for the development of T2DM, and they may be risk factors for T2DM.
BackgroundS. aethiopicum is a close relative to S. melongena and has been routinely used to improve disease resistance in S. melongena. However, these efforts have been greatly limited by the lack of a reference genome and the clear understanding of the genes involved during biotic and abiotic stress response. ResultsWe present here a draft genome assembly of S. aethiopicum of 1.02 Gb in size, which is predominantly occupied by repetitive sequences (76.2%), particularly long terminal repeat elements. We annotated 37,681 gene models including 34,905 protein-coding genes. We observed an expansion of resistance genes through two rounds of amplification of LTR-Rs, occurred around 1.25 and 3.5 million years ago, respectively. The expansion also occurred in gene families related to drought tolerance. A number of 14,995,740 SNPs are identified by re-sequencing 65 S. aethiopicum genotypes including "Gilo" and "Shum" accessions, 41,046 of which are closely linked to resistance genes. The domestication and demographic history analysis reveals selection of genes involved in drought tolerance in both "Gilo" and "Shum" groups. A pan-genome of S. aethiopicum with a total of 36,250 protein-coding genes was assembled, of which 1,345 genes are missing in the reference genome. ConclusionsOverall, the genome sequence of S. aethiopicum increases our understanding of the genomic mechanisms of its extraordinary disease resistance and drought tolerance. The SNPs identified are available for potential use by breeders. The information provided here will greatly accelerate the selection and breeding of the African eggplant as well as other crops within the Solanaceae family.
CREBBP mutations are highly recurrent in B-cell lymphomas and either inactivate its histone acetyltransferase (HAT) domain or truncate the protein. Herein, we show that these two classes of mutations yield different degrees of disruption of the epigenome, with HAT mutations being more severe and associated with inferior clinical outcome. Genes perturbed by CREBBP mutation are direct targets of the BCL6/HDAC3 onco-repressor complex. Accordingly, we show that HDAC3 selective inhibitors fully reverse CREBBP mutant aberrant epigenetic programming resulting in: a) growth inhibition of lymphoma cells through induction of BCL6 target genes such as CDKN1A and b) restoration of immune surveillance due to induction of BCL6 repressed IFN pathway and antigen presentation genes. By reactivating these genes, exposure to HDAC3-i restored the ability of tumor infiltrating lymphocytes to kill DLBCL cells in an MHC II and MHC I dependent manner. Hence HDAC3-i represent a novel mechanism-based immune-epigenetic therapy for CREBBP mutant lymphomas. STATEMENT OF SIGNIFICANCEWe have leveraged the molecular characterization of different types of CREBBP mutations to define a rational approach for targeting these mutations through selective inhibition of HDAC3. This represents an attractive therapeutic avenue for targeting synthetic vulnerabilities in CREBBP mutant cells in tandem with promoting anti-tumor immunity.
Consistent codon usage patterns across species was supposed to be observed owing to the degeneracy of genetic code and the conservation of the translation machinery. In fact, however, codon usage vary dramatically among organisms, and the choice difference might also affect downstream protein expressions, structures as well as their functions. It is suggested that different codon usage patterns should encrypt distinct characters for a certain type of organism, and as a result, a series of machine-learning models have been constructed, not only for learning the patterns from certain species, but also for predicting the species based on given patterns. Two gene segments of influenza A virus, hemagglutinin (HA; gene 4) and neuraminidase (NA; gene 6), were so essential for the immune response of their hosts, that the serotypes of the viruses are named after their combinations. They thus become the objects of this study, and those proposed models work quite well on the designated tasks.
Black rockfish (Sebastes schlegelii) is a teleost species where eggs are fertilized internally and retained in the maternal reproductive system, where they undergo development until live birth (termed viviparity). In the present study, we report a chromosome-level black rockfish genome assembly. High-throughput transcriptome analysis (RNA-seq and ATAC-seq), coupled with in situ hybridization (ISH) and immunofluorescence, identify several candidate genes for maternal preparation, sperm storage and release, and hatching. We propose that zona pellucida (ZP) genes retain sperm at the oocyte envelope, while genes in two distinct astacin metalloproteinase subfamilies serve to release sperm from the ZP and free the embryo from chorion at pre-hatching stage. Finally, we present a model of black rockfish reproduction, and propose that the rockfish ovarian wall has a similar function to uterus of mammals. Taken together, these genomic data reveal unprecedented insights into the evolution of an unusual teleost life history strategy, and provide a sound foundation for studying viviparity in non-mammalian vertebrates and an invaluable resource for rockfish ecology and evolution research.
Asparagus bean (Vigna. unguiculata ssp. sesquipedialis), known for its very long and tender green pods, is an important vegetable crop broadly grown in the developing countries. Despite its agricultural and economic values, asparagus bean does not have a high-quality genome assembly for breeding novel agronomic traits. In this study, we reported a high-quality 632.8 Mb assembly of asparagus bean based on the whole genome shotgun sequencing strategy. We also generated a high-density linkage map for asparagus bean, which helped anchor 94.42% of the scaffolds into 11 pseudo-chromosomes. A total of 42,609 protein-coding genes and 3,579 non-protein-coding genes were predicted from the assembly. Taken together, these genomic resources of asparagus bean will facilitate the investigation of economically valuable traits in a variety of legume species, so that the cultivation of these plants would help combat the protein and energy malnutrition in the developing world.
Sexual dimorphism like dioecy (separate male and female individuals) have evolved in diverse multicellular eukaryotes while the molecular mechanisms underlying the development of such a key biological trait remains elusive (1). The living fossil Ginkgo biloba represents an early diverged lineage of land plants with dioecy. However, its sex-determination system and molecular basis have long been controversial or unknown. In the present research, we assembled the first and largest to date chromosome-level genome of a non-model tree species using Hi-C data. With this reference genome, we addressed both questions using genome resequencing data gathered from 97 male and 265 female trees of ginkgo, as well as transcriptome data from three developmental stages for both sexes. Our results support vertebrate-like XY chromosomes for ginkgo and five potential sex-determination genes, which may originate ~14 million years ago. This is the earliest diverged sex determination region in all reported plants as yet. The present research resolved a long-term controversy, lay a foundation for future studies on the origin and evolution of plant sexes, and provide genetic markers for sex identification of ginkgo which will be valuable for both nurseries and field ecology of ginkgo.
Calorie restriction (CR), which has the potential effect to weight loss and blood amino acids, has been demonstrated to associate with gut microbiota in human, especially in obese individuals. However, studies for simultaneously evaluating enterotype-dependent impacts of CR on the gut microbiota and blood amino acids in nonobese individuals are still limited.\n\nHere, 41 nonobese individuals received a 3-week CR diet with approximately 50% fewer calories than normal diet. We measured their BMI and blood amino acid concentration, along with the gut microbiota before and after the intervention. In this trial, 28 Enterotype Bacteroides (ETB) subjects and 13 Enterotype Prevotella (ETP) subjects were identified before the intervention. Short-term CR dietary intervention decreased the body mass index (BMI) in most subjects but varied in subjects with different enterotypes. ETP subjects exhibited significantly higher BMI loss ratio than the ETB subjects. CR additionally induced substantial enterotype-independent changes in blood amino acids, but only minor changes in gut microbial composition.\n\nWe further built a prediction model based on baseline relative abundances of 7 gut microbial species showing high performance in predicting CR-associated BMI loss ratio. Among them, the relative abundance of ETB-enriched Clostridium bolteae and C. ramosum were negatively correlated with BMI loss ratio while the relative abundance of Dorea longicatena which was slightly enriched in ETP subjects, was positively correlated with BMI loss ratio.\n\nTogether, our work points out that the individual variation of BMI loss after CR could be partially correlated with different microbial composition and highlights the potential application for microbiome stratification in personalized nutrition intervention.
Currently, over 20 genes have been defined that can confer susceptibility for high-risk breast cancer. Although research has proved the utility of multiple-gene sequencing in the assessment of breast cancer risk, there is little data from China patients. Here, we use a multiple-gene sequencing panel to identify the variant spectrum in Chinese high-risk breast cancer subjects.\n\nA total of 829 Chinese high-risk breast cancer patients participated in the research. The coding regions of 115 hereditary cancer susceptibility genes were sequenced using a next generation sequencing platform. In total, 193 pathogenic variants were identified in 45 genes from 177 patients. The pathogenic variant carrier rate is 21.4%: with 10.5% patients carrying a BRCA1 or BRCA2 mutation only, 10.0% of patients carried non-BRCA gene mutations only, while 1.0% of patients carried both a BRCA1/2 and a non-BRCA gene mutation. Variants of uncertain significance (VUS) totaling 2632 were identified in 115 genes from 787 of 829 patients: 82.5% patients carried more than one VUS, and only 5.1% patients did not carry any VUS. Families carrying pathogenic variants were tracked and adenoma was founded in three of them. Our data provide a comprehensive analysis of potential susceptibility variations of high-risk for breast cancer in a Chinese population. This data will be useful for the comparison of the susceptibility variation spectrum between different populations and to discover potential pathogenic variants to improve the prevention and treatment of high-risk breast cancer.
Long non-coding RNAs (lncRNAs) play key roles in various biological processes. However, the roles of lncRNAs in macrophage polarization remain largely unexplored. In this study, thousands of lncRNAs were identified that are differentially expressed in distinct polarized bone marrow-derived macrophages (BMDMs). Among them, Dnmt3aos (DNA methyltransferase 3A, opposite strand), as a known lncRNA, locates on the antisense strand of Dnmt3a. Functional experiments further confirmed that Dnmt3aos were highly expressed in M(IL-4) macrophages and participated in the regulation of Dnmt3a expression, and played a key role in macrophage polarization. The DNA methylation profiles between the Dnmt3aos knockdown group and the control group in M(IL-4) macrophages were determined by MeDIP-seq technique for the first time, and the Dnmt3aos-Dnmt3a axis-mediated DNA methylation modification-regulated macrophage polarization related gene IFN-{gamma} was identified. Our study will help to enrich our knowledge of the mechanism of macrophage polarization and will provide new insights for immunotherapy in macrophage-associated diseases.
Cyclins are central engines of cell cycle progression when partnered with Cyclin Dependent Kinases (CDKs). Among the different cyclins controlling cell cycle progression, cyclin F does not partner with a CDK, but forms an E3 ubiquitin ligase, assembling through the F-box domain, an Skp1-Cul1-F-box (SCF) module. Although multiple substrates of cyclin F have been identified the vulnerabilities of cells lacking cyclin F are not known. Thus, we assessed viability of cells lacking cyclin F upon challenging cells with more than 200 kinase inhibitors. The screen revealed a striking synthetic lethality between Chk1 inhibition and cyclin F loss. Chk1 inhibition in cells lacking cyclin F leads to DNA replication catastrophe. The DNA replication catastrophe depends on the accumulation of E2F1 in cyclin F depleted cells. We observe that SCFcyclin F promotes E2F1 degradation after Chk1 inhibitors in a CDK dependent manner. Thus, Cyclin F restricts E2F1 activity during cell cycle and upon checkpoint inhibition to prevent DNA replication stress. Our findings pave the way for patient selection in the clinical use of checkpoint inhibitors.
PurposeConcurrent newborn hearing and genetic screening has been reported, but its benefits have not been statistically proven due to limited sample sizes and outcome data. To fill this gap, we analyzed outcomes of a large number of newborns with genetic screening results.\n\nMethodsNewborns in China were screened for 20 hearing-loss-related genetic variants from 2012-2017. Genetic results were categorized as positive, at-risk, inconclusive, or negative. Hearing screening results, risk factors, and up-to-date hearing status were followed-up via phone interviews.\n\nResultsWe completed genetic screening on one million newborns and followed up 12,778. We found that a positive genetic result significantly indicated a higher positive predictive value of the initial hearing screening (60% vs. 5.0%, P<0.001) and a lower rate of loss-to-follow-up (5% vs. 22%, P<0.001) than an inconclusive one. Importantly, 42% of subjects in the positive group with reported or presymptomatic hearing loss were \"missed\" by conventional hearing screening. Furthermore, genetic screening identified 0.23% of subjects predisposed to preventable ototoxicity.\n\nConclusionOur results demonstrate that limited genetic screening identified additional cases, reduced loss-to-follow-up, and informed families of ototoxicity risks, providing convincing evidence to support integrating genetic screening into universal newborn hearing screening programs.
Understanding the risk perception of pandemic influenza can improve the risk communication efficiency of the government and ultimately reduce losses caused by the disaster. A mental model interview of 28 individuals who discussed pandemic influenza was analyzed in this paper. The interviewees were college students in Beijing, China who were evaluated to understand their views on the risk perception of pandemic influenza. Referring to the mental model theory, the researchers using Delphi method to identify the key risk factors and concepts to examine the public understanding of these contents; then, the researchers identify the deviations in their understanding so that suggestions and countermeasures have been put forward to enhance the effectiveness of risk communication. Most of the conceptual content was mentioned by most interviewees. However, some interviewees showed misunderstanding including excessive optimism about the consequences of pandemic influenza, a lack of detailed mitigation measures, and negative attitudes toward health education and vaccination. Once faced with threats, this may lead to the failure of risk communication. In Beijing City, the center of domestic and international education, the historical SARS epidemic and this years seasonal flu peak are all hints of the potential risk of a pandemic outbreak. Beijings college students one-sided understanding and misunderstanding of the relevant risk information may increase the risk during an influenza pandemic. The results highlight the necessity for the government to clearly focus on the communication content of the student group, provide an official reference plan for the public and update health education on this topic.
Genome editing tools including CRISPR/Cas9 and base editors hold great promise for correcting pathogenic mutations. Unbiased genome-wide off-target effects of the editing in mammalian cells is required before clinical applications, but determination of the extent of off-target effects has been difficult due to the existence of single nucleotide polymorphisms (SNPs) in individuals. Here, we developed a method named GOTI (Genome-wide Off-target analysis by Two-cell embryo Injection) to detect off-target mutations without interference of SNPs. We applied GOTI to both the CRISPR-Cas9 and base editing (BE3) systems by editing one blastomere of the two-cell mouse embryo and then compared whole genome sequences of progeny-cell populations at E14.5 stage. Sequence analysis of edited and non-edited cell progenies showed that undesired off-target single nucleotide variants (SNVs) are rare (average 10.5) in CRISPR-edited mouse embryos, with a frequency close to the spontaneous mutation rate. By contrast, BE3 editing induced over 20-fold higher SNVs (average 283), raising the concern of using base-editing approaches for biomedical application.
BackgroundWhole exome sequencing (WES) has been widely used in human genetics research. BGISEQ-500 is a recently established next-generation sequencing platform. However, the performance of BGISEQ-500 on WES is not well studied. In this study, we evaluated the performance of BGISEQ-500 on WES by side-to-side comparison with Hiseq4000, on wellcharacterized human sample NA12878.\n\nResultsBGISEQ demonstrated similarly high reproducibility as Hiseq for variation detection. Also, the SNPs from BGISEQ data is highly consistent with Hiseq results (concordance 96.5%[~]97%). Variation detection accuracy was subsequently evaluated with data from the genome in a bottle project as the benchmark. Both platforms showed similar sensitivity and precision in SNP detection. While in indel detection, BGISEQ showed slightly higher sensitivity and lower precision. The impact of sequence depth and read length on variation detection accuracy was further analyzed, and showed that variation detection sensitivity still increasing when the sequence depth is larger than 100x, and the impact of read length is minor when using 100x data.\n\nConclusionsThis study suggested that BGISEQ-500 is a qualified sequencing platform for WES.
Plant height is an important component of plant architecture and significantly affects crop breeding practices and yield. We obtained a few segregated dwarf soybeans in the populations derived from the crossing of Glycine max var. Peking and Glycine soja var. IT182936 in an F5 RIL population. These dwarf soybeans may be useful genetic resources for plant breeders, geneticists and biologists. We attempted to find differentially expressed genes to classify and understand the regulation of genes related to plant growth in mutant dwarf soybeans, which appeared in the F5 generation. Using the Illumina high-throughput platform, transcriptomes were generated and compared among normal and dwarf soybeans in triplicate. We found complex relationship of the expressed genes to plant growth. There are highly significantly up-/downregulated genes according to the comparison of gene expression in normal and dwarf soybeans. The genes related to disease and stress responses were found to be upregulated in dwarf soybeans. Such over-expression of disease resistance and other immune response genes was targeted to understand how the immune genes regulate the response of plant growth. In addition, photosynthesis-related genes showed very low expression in dwarf lines. The transcriptome expression and genes classified as related to plant growth may be useful resources to researchers studying plant growth.