Associate Professor of Biomedical Engineering Advanced Innovation Center, Beihang University, Member of Youth Innovation Promotion Association, Chinese Academy of Sciences.
IFN-alpha-mediated Base Excision Repair Pathway Correlates with Antiviral Response Against Hepatitis B Virus Infection
Hepatology, 2016
Previous studies identified APOBEC deaminases as enzymes targeting hepatitis B virus (HBV) DNA in... more Previous studies identified APOBEC deaminases as enzymes targeting hepatitis B virus (HBV) DNA in the nucleus thus affecting its persistence. Interferon (IFN)-α treated chimpanzees and hepatitis C patients showed elevated APOBEC expression. We thus hypothesized that the responses to IFN-α treatment of chronic hepatitis B (CHB) patients is influenced by IFN-induced base excision repair (BER). CHB-treatment naïve patients, patients treated with PEGylated IFN-α, and patients with sequential treatment of Entecavior and PEGylated IFN-α were recruited. Blood and liver biopsy samples were collected before treatment and at treatment endpoint. BER genes were assessed by quantitative RT-PCR. BER gene expression levels and IFN treatment responses were correlated in patient liver biopsies. APOBEC3A,-B,-C,-D/E, and-G mRNA levels were up-regulated in IFN-treated patients. APOBEC3A expression was significantly higher in IFN-responders than in non-responders. BER genes NEIL3 was down-regulated in IFN-treated pa tients. APOBEC3 and BER gene expression at treatment endpoints partially correlated with the corresponding absolute DNA level or degree of HBsAg and HBV DNA decline. Our study suggests that the expression of APOBEC3A positively correlates with IFN-treatment responses in CHB patients, while NEIL3 shows negative correlation. These genes may involve to IFN mediated viral suppression and serve as biomarkers for CHB disease management
Additional file 8 of Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing
Additional file 8. Table S7. MethylHBV5k and top 5 selected regions of 58 cfDNA samples from vali... more Additional file 8. Table S7. MethylHBV5k and top 5 selected regions of 58 cfDNA samples from validation cohort by resampling 10 M single reads.
Additional file 4 of Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing
Additional file 4:. Table S3. The coordinates of the extracted HBV integration sites.
Additional file 5 of Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing
Additional file 5:. Table S4. Clinical information of 54 individuals by low-pass WGBS.
Background: Myopia is a good model for understanding the interaction between genetics and environ... more Background: Myopia is a good model for understanding the interaction between genetics and environmental stimuli. Here we dissect the biological processes affecting myopia progression. Methods: Human Genetic Analyses: (1) gene set analysis (GSA) of new genome wide association study (GWAS) data for 593 individuals with high myopia (refraction-6 diopters [D]); (2) over-representation analysis (ORA) of 196 genes with de novo mutations, identified by whole genome sequencing of 45 highmyopia trio families, and (3) ORA of 284 previously reported myopia risk genes. Contributions of the enriched signaling pathways in mediating the genetic and environmental interactions during myopia development were investigated in vivo and in vitro. Results: All three genetic analyses showed significant enrichment of four KEGG signaling pathways, including amphetamine addiction, extracellular matrix (ECM) receptor interaction, neuroactive ligand-receptor interaction, and regulation of actin cytoskeleton pathways. In individuals with extremely high myopia (refraction-10 D), the GSA of GWAS data revealed significant enrichment of the HIF-1a signaling pathway. Using human scleral fibroblasts, silencing the key nodal genes within protein-protein interaction networks for the enriched pathways antagonized the hypoxia-induced increase in myofibroblast transdifferentiation. In mice, scleral HIF-1a downregulation led to hyperopia, whereas upregulation resulted in myopia. In human subjects, near work, a risk factor for myopia, significantly decreased choroidal blood perfusion, which might cause scleral hypoxia.
Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis that presents as a cli... more Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis that presents as a clinical triad including follicular hamartomas, renal neoplasms and lung cysts associated with an increased risk of pneumothorax. FLCN gene defects have been identified as being responsible for BHDS. We herein report the case of a 67-year-old woman with the full-blown BHDS phenotype, characterized by skin lesions, multiple lung bullae and renal neoplasms. In her family history, one of the patient's sons exhibited a similar phenotype, without renal neoplasms. Due to the relatively late age of onset of renal neoplasms among variable BHDS phenotypes, follow-up imaging is recommended for the son who has not yet developed renal neoplasms.
Besides mosquitoes, ticks are regarded as the primary source of vector-borne infectious diseases.... more Besides mosquitoes, ticks are regarded as the primary source of vector-borne infectious diseases. Indeed, a wide variety of severe infectious human diseases, including those involving viruses, are transmitted by ticks in many parts of the world. To date, there are no published reports on the use of next-generation sequencing for studying viral diversity in ticks or discovering new viruses in these arthropods from China. Here, Ion-torrent sequencing was used to investigate the presence of viruses in three Rhipicephalus spp. tick pools (NY-11, NY-13, and MM-13) collected from the Menglian district of Yunnan, China. The sequencing run resulted in 3,641,088, 3,106,733, and 3,871,851 reads in each tick pool after trimming. Reads and assembled contiguous sequences (contigs) were subject to basic local alignment search tool analysis against the GenBank database. Large numbers of reads and contigs related to known viral sequences corresponding to a broad range of viral families were identif...
Constructing an initial map of transmission distortion based on high density HapMap SNPs across the human autosomes
Journal of Genetics and Genomics, 2009
Transmission distortion (TD) is a significant departure from Mendelian predictions of genes or ch... more Transmission distortion (TD) is a significant departure from Mendelian predictions of genes or chromosomes to offspring. While many biological processes have been implicated, there is still much to be understood about TD in humans. Here we present our findings from a genome-wide scan for evidence of TD using haplotype data of 60 trio families from the International HapMap Project. Fisher's exact test was applied to assess the extent of TD in 629,958 SNPs across the autosomes. Based on the empirical distribution of P(Fisher) and further permutation tests, we identified 1,205 outlier loci and 224 candidate genes with TD. Using the PANTHER gene ontology database, we found 19 categories of biological processes with an enrichment of candidate genes. In particular, the "protein phosphorylation" category contained the largest number of candidates in both HapMap samples. Further analysis uncovered an intriguing non-synonymous change in PPP1R12B, a gene related to protein phosphorylation, which appears to influence the allele transmission from male parents in the YRI (Yoruba from Ibadan, Nigeria) population. Our findings also indicate an ethnicity-related property of TD signatures in HapMap samples and provide new clues for our understanding of TD in humans.
Additional file 1 of Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing
Additional file 1:. Fig. S1. Methylation profiling of 5 pilot cfDNA samples with relative high-de... more Additional file 1:. Fig. S1. Methylation profiling of 5 pilot cfDNA samples with relative high-depth WGBS. Fig. S2. The percentage and enrichment score of DMCs inside and outside CpG islands at different genomic elements. Fig. S3. The average DNA methylation level profiles along 10 kb upstream and downstream of the HBV integration sites in all the tumor tissues and paired buffy coat samples. Fig. S4. The difference between buffy coat and tumor tissue of Methylgenome, MethylHBV, MethylAlu and MethylLINE. Fig. S5. The efficiency of re-sampling sequencing reads for low pass WGBS in 5 pilot cfDNA samples. Fig. S6. The enrichment scores of CpGs at different genomic elements by total sequencing reads from published dataset. Fig. S7. ROC curves for HCC detection using hypomethylation around HBV integration regions.
Applications and potentials of nanopore sequencing in the (epi)genome and (epi)transcriptome era
The Innovation, 2021
Summary The Human Genome Project opened an era of (epi)genomic research, and also provided a plat... more Summary The Human Genome Project opened an era of (epi)genomic research, and also provided a platform for the development of new sequencing technologies. During and after the project, several sequencing technologies continue to dominate nucleic acid sequencing markets. Currently, Illumina (short-read), PacBio (long-read), and Oxford Nanopore (long-read) are the most popular sequencing technologies. Unlike PacBio or the popular short-read sequencers before it, which, as examples of the second or so-called Next-Generation Sequencing platforms, need to synthesize when sequencing, nanopore technology directly sequences native DNA and RNA molecules. Nanopore sequencing, therefore, avoids converting mRNA into cDNA molecules, which not only allows for the sequencing of extremely long native DNA and full-length RNA molecules but also document modifications that have been made to those native DNA or RNA bases. In this review on direct DNA sequencing and direct RNA sequencing using Oxford Nanopore technology, we focus on their development and application achievements, discussing their challenges and future perspective. We also address the problems researchers may encounter applying these approaches in their research topics, and how to resolve them.
As the best adapted high altitude population, Tibetans feature a relatively high offspring surviv... more As the best adapted high altitude population, Tibetans feature a relatively high offspring survival rate. Genome-wide studies have identified hundreds of candidate SNPs related to high altitude adaptation of Tibetans, although most of them have unknown functional relevance. To explore the mechanisms behind successful reproduction at high altitudes, we compared the placental transcriptomes of Tibetans, sea level Hans (SLHan), and Han immigrants (ImHan). Among the three populations, placentas from ImHan showed a hyperactive gene expression pattern. Their increased activation demonstrates a hypoxic stress response similar to sea level individuals experiencing hypoxic conditions. Unlike ImHan, Tibetan placentas were characterized by the significant up-regulation of placenta-specific genes, and the activation of autophagy and the tricarboxylic acid (TCA) cycle. Certain conserved hypoxia response functions, including the antioxidant system and angiogenesis, were activated in both ImHan an...
Chordoma is a rare bone tumor arising from notochordal remnants, but the underlying mechanism rem... more Chordoma is a rare bone tumor arising from notochordal remnants, but the underlying mechanism remains elusive. By integrated mRNA and microRNA analyses, we found significant downregulation of TGFB3 along with upregulation of its inhibitor, miR-29 family in chordoma comparing with notochord. Somatic copy number gains of miR-29 loci in chordoma highlighted a mechanism of inactivation of TGFB3 signaling in tumor formation. In zebrafish, knockout and knockdown homologous tgfb3 resulted in a chordoma-like neoplasm. On the other hand, Smad7 negative feedback regulation of transforming growth factor-β (TGF-β) signaling is retentive in chordoma cell UM-Chor1 despite its disruption in most cancer cells (e.g. A549). Therefore, contrary to other cancers, exogenous TGF-β activated Smad7 by downregulating miR-182 and inhibited cell migration and invasion in UM-Chor1. Meanwhile, TGF-β decreased chordoma characteristic protein Brachyury. Altogether, downregulation of TGFB3 causes chordomagenesis, ...
Additional file 6 of Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing
Additional file 6:. Table S5. The statistical information of 54 cfDNA samples by low-pass WGBS.
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Papers by Dake Zhang