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| 1 | Antibody upstream sequence diversity and its biological implications revealed by repertoire sequencing显示文摘The sequence upstream of the antibody variable region(antibody upstream sequence[AUS])consists of a 5′untranslated region(5′UTR)and a preceding leader region.The sequence variations in AUS affect antibody engineering and PCR based antibody quantification and may also be implicated in mRNA transcription and translation.However,the diversity of AUSs remains elusive.Using 5′rapid amplification of cDNA ends and high-throughput antibody repertoire sequencing technique,we acquired full-length AUSs for human,rhesus macaque,cynomolgus macaque,mouse,and rat.We designed a bioinformatics pipeline and identified 3307 unique AUSs,corresponding to 3026 and 1457 unique sequences for 5′UTR and leader region,respectively.Comparative analysis indicated that 928(63.69%)leader sequences are novel relative to those recorded in the international ImMunoGeneTics information system.Evolutionarily,leader sequences are more conserved than 5′UTR and seem to coevolve with their downstream V genes.Besides,single-nucleotide polymorphisms are position dependent for leader regions and may contribute to the functional reversal of the downstream V genes.Finally,the AUGs in AUSs were found to have little impact on gene expression.Taken together,our findings can facilitate primer design for capturing antibodies efficiently and provide a valuable resource for antibody engineering and molecule-level antibody studies. | Yan Zhu Xiujia Yang Cuiyu Ma Haipei Tang Qilong Wang Junjie Guan Wenxi Xie Sen Chen Yuan Chen Minhui Wang Chunhong Lan Deqiang Sun Lai Wei Caijun Sun Xueqing Yu Zhenhai Zhang | 2021 | Journal of Genetics and Genomics2021，48，10： | 0 |
| 2 | The Biological Significance of Multi-copy Regions and Their Impact on Variant Discovery显示文摘Identification of genetic variants via high-throughput sequencing(HTS)technologies has been essential for both fundamental and clinical studies.However,to what extent the genome sequence composition affects variant calling remains unclear.In this study,we identified 63,897 multi-copy sequences(MCSs)with a minimum length of 300 bp,each of which occurs at least twice in the human genome.The 151,749 genomic loci(multi-copy regions,or MCRs)harboring these MCSs account for 1.98% of the genome and are distributed unevenly across chromosomes.MCRs containing the same MCS tend to be located on the same chromosome.Gene Ontology(GO)analyses revealed that 3800 genes whose UTRs or exons overlap with MCRs are enriched for Golgirelated cellular component terms and various enzymatic activities in the GO biological function category.MCRs are also enriched for loci that are sensitive to neocarzinostatin-induced double-strand breaks.Moreover,genetic variants discovered by genome-wide association studies and recorded in dbSNP are significantly underrepresented in MCRs.Using simulated HTS datasets,we show that false variant discovery rates are significantly higher in MCRs than in other genomic regions.These results suggest that extra caution must be taken when identifying genetic variants in the MCRs via HTS technologies. | Jing Sun Yanfang Zhang Minhui Wang Qian Guan Xiujia Yang Jin Xia Ou Mingchen Yan Chengrui Wang Yan Zhang Zhi-Hao Li Chunhong Lan Chen Mao Hong-Wei Zhou Bingtao Hao Zhenhai Zhang | 2020 | Genomics, Proteomics & Bioinformatics2020，18，5： | 0 |
| 3 | Correlation of hair risperidone concentration and serum level among patients with schizophrenia显示文摘Background Risperidone (RSP) has a rapid onset in vivo, low dosage and high plasma protein binding rate, therefore therapeutic drug monitoring (TDM) is needed to ensure safety in clinical treatment. However, compared with blood, hair is non-invasive, safe, non-infectious and easy to transport and store. Aims This study aims to investigate the correlations among the drug concentrations of RSP in hair and serum, which provides an experimental basis to explore hair as a novel biomaterial to meet the needs of clinical detection. Methods 34 patients with schizophrenia treated with RSP for more than 3 months were enrolled in this study. About 1 cm section of hair near the scalp was taken from the subjects, pretreated and detected by liquid chromatography-mass spectrometry. A correlation analysis was conducted among the drug concentrations in hair, the serum concentrations and the daily dosage. The data were analysed usi叩 SPSS 20.0 software. Results There was significant correlation between the hair concentration of RSP (two-tailed test, r=0.440, p=0.009) with the serum concentration of RSP, and the hair concentration of 9-hydroxyrisperidone (9-HR) with the serum concentration of 9-HR had no significant correlation (two-tailed test, r=-0.217, p=0.217);the total concentration of the RSP and 9-HR had no significant correlation between hair and serum (r=0.227, p=0.196). The dosage had no statistically significant correlation with the concentration of RSP in hair (r=0.207, p=0.241), 9-HR in hair (r=-0.194, p=0.271) and the total concentration of RSP and 9-HR in hair (r=0.188, p=0.288). There was no statistical correlation between the dosage and the concentration of RSP in serum (r=-0.059, p=0.741), but significant correlation between the dosage and 9-HR in serum (r=0.581 p<0.001) was found, and the correlation between the dosage and the total concentration of the two drugs RSP and 9-HR in serum was also significant (r=0.437, p=0.01). Conclusion The correlation analysis showed that the concentration of RSP in hair was statistically significant with the serum RSP concentration. In this study, we provided some experimental basis for hair as a new biomaterial to monitor the therapeutic drug concentration. | Xiujia Sun Lihua Wang Fuzhong Yang Juanjuan Ren Ping Jiang Hongmei Liu Huafang Li Chunbo Li Chen Zhang | 2019 | General Psychiatry2019，32，1： | 0 |
| 4 | Effects of the combination of second-generation antipsychotics on serum concentrations of aripiprazole and dehydroaripiprazole in Chinese patients with schizophrenia显示文摘Background Aripiprazole(ARI)is often prescribed alone or in combination with other second-generation antipsychotics(SGAs)to treat patients with schizophrenia.However,this may increase the potential clinical significance of drug-drug interactions.Therapeutic drug monitoring(TDM)is an important and fundamental tool both when administering ARI alone and in combination with other SGAs to monitor ARI pharmacokinetics,adjust the dosage and thereby achieve more effective and safer treatment.Aims This study retrospectively investigated the effects of four SGA comedications(clozapine,risperidone,quetiapine(QTP)and olanzapine)and other potential factors(sex,age and ARI dose)on the serum concentrations of ARI and dehydroaripiprazole(DARI)in Chinese patients with schizophrenia using TDM data.Methods High-performance liquid chromatography was used to test the serum concentrations of ARI,DARI and ARI+DARI.In addition,steady-state dose-adjusted serum concentrations(ie,concentration-to dose ratios,C:D ratios)of ARI,DARI and ARI+DARI;sex;age;ARI dose and SGA comedication dose between 299 inpatients with schizophrenia who received ARI or SGA comedication were all collected and analysed.Spearman’s correlation and multiple linear regression analysis were used to evaluate bivariate associations between ARI dose and serum ARI and DARI concentrations and describe the effect of independent variables on serum ARI and DARI concentrations,respectively.Results There were significant differences in the C:D ratios of ARI(χ^(2)=−3.21,p=0.001)and ARI+DARI(χ^(2)=−2.50,p=0.01)between the ARI and SGA groups,as well as in the C:D ratios of ARI(χ^(2)=−3.59,p<0.001)and ARI+DARI(χ^(2)=−3.10,p=0.002)between the female patients in the two groups.Of the four SGAs,only QTP had significant effects on the C:D ratios of ARI(Z=−4.12,p<0.001)and ARI+DARI(Z=−3.62,p<0.001)when compared with the ARI group in the whole sample and on the C:D ratios of ARI,DARI and ARI+DARI(Z=−3.96,p<0.001;Z=−2.22,p=0.03;Z=−3.75,p<0.001,respectively)in women when compared with their counterparts in the ARI group.Conclusion Comedication with SGAs resulted in lower C:D ratios of ARI and ARI+DARI compared with ARI monotherapy,and comedication with QTP resulted in lower C:D ratios of ARI and ARI+DARI than ARI monotherapy.Despite this statistical significance of our findings,whether the presently observed effect has clinical significance requires exploration by further research.TDM and dosage regulation of ARI should be performed in Chinese inpatients with schizophrenia who are receiving SGA comedication(especially QTP)to maintain a safe and effective dose-adjusted serum concentration of ARI and DARI. | Ping Jiang Xiujia Sun Juanjuan Ren Hongmei Liu Zhiguang Lin Junwen Liu Xinyu Fang Chen Zhang | 2021 | General Psychiatry2021，34，2： | 0 |
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