{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/checksum.txt"],"Raw":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/XC02740DA_C1.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/XC02740DA_C3.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/XC02740DA_B3.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/XC02740DA_A2.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/XC02740DA_D2.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/XC02740DA_D3.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/XC02740DA_D1.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/XC02740DA_C2.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/XC02740DA_B1.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/XC02740DA_A1.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/XC02740DA_B2.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/XC02740DA_A3.raw"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD066939/Results.zip"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["ymjy296@163.com"],"submitter":["Chen Yimin"],"technology_type":["Mass Spectrometry","Bottom-up proteomics"],"software":[""],"submitter_keywords":["Gene mutation","Proteomics","Chb","Non-targeted metabolomics","Genomics analysis"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD066939"],"tissue":["Blood Serum"],"sample_protocol":["The study sample comprises patients diagnosed with chronic hepatitis B who were admitted to the Infectious Diseases Department at Jiaxing First Hospital between December 1, 2023, and December 31, 2024. All participants satisfied the most recent diagnostic criteria established in China and were aged 18 years or older. Informed consent was obtained from all participants prior to their inclusion in the study. Exclusion criteria included a history of the following conditions within six months prior to enrollment: mixed liver disease, co-infection with other viruses (such as hepatitis A virus, HCV, or HDV), primary hepatocellular carcinoma or other malignancies, autoimmune or immune-mediated diseases, organ transplantation, diabetes mellitus, hyperthyroidism, pregnancy, neuropsychiatric disorders, or severe cardiac, hepatic, or renal dysfunction.Through genomic sequencing of serum viral DNA in the BCP/PC region of all patients, and after excluding samples with substantial missing data, we ultimately included a total of 108 patients. These patients were categorized into four groups: Group A (wild strain, WT=27), Group B (G1896A=27), Group C (A1762T/G1764A=27), and Group D (A1762T/G1764A+ G1896A=27). The clinical information of the patients is presented in Table 1. This study was conducted in strict accordance with the provisions and principles of the Declaration of Helsinki, with written informed consent obtained from all participants. Additionally, the use of human serum and biopsy samples was approved by the Ethics Committee of the Affiliated Hospital of Jiaxing University (2024-KY-720)."],"repository":["Pride"],"quantification_method":["Not available"],"modification":[""],"data_protocol":["Clinical Data The clinical data were analyzed using SPSS 22.0 (IBM Corp., Armonk, USA). Categorical variables were compared using the χ2 test and described in terms of the percentage. For continuous variables, the normal distribution was determined using the Kolmogorov−Smirnov test. Data with normal distribution were analyzed using Student’s t-test and presented as mean ± standard deviation. Non-normally distributed data were analyzed using the Mann−Whitney U test and described in terms of the median with an interquartile range. Metabolomics Data The metabolites underwent unsupervised principal component analysis (PCA) utilizing the prcomp function, which elucidated the separation and aggregation patterns of metabolites both between and within groups. The Pearson correlation coefficient (PCC) among samples was computed using the cor function in R and visualized through a heatmap. Concurrently, hierarchical cluster analysis (HCA) and PCC were performed using the R package ComplexHeatmap. A partial least squares discriminant analysis (OPLS-DA) model was developed via partial least squares regression to determine the variable importance in projection (VIP), which assesses the significance and explanatory capacity of each metabolite expression pattern across the groups. Univariate analysis was conducted employing fold change (FC) and Student's t-test, with the false discovery rate (FDR) adjusted using the Benjamini-Hochberg method to derive q values. A volcano plot was employed to depict the distribution of metabolite ions, with ions meeting the criteria of FC ≥ 2 or FC ≤ 1/2 and a q value < 0.05 deemed significant. Metabolites with VIP scores ≥ 1 were identified as differential metabolites. Proteomic data In this study, DIA data were acquired utilizing the Pulsar search engine integrated within Spectronaut (version 18), employing the software's default parameters. Comparative analysis of these proteins was conducted using BLAST, and their sequences were annotated by clustering protein homologous clusters to deduce their functions. Subcellular localization of the proteins was also ascertained. The relative quantitative values of each protein across the comparison samples were assessed using the t-test, and corresponding P-values were computed. Proteins exhibiting a fold change (FC) greater than 1.5 or less than 0.67, with a P-value below 0.05, were designated as differentially expressed proteins (DEPs). These DEPs were visualized using a volcano plot, and their relative abundance in each individual was examined through cluster analysis. Subsequently, gene ontology (GO) analysis was conducted on the DEPs using InterProScan software to elucidate their biological functions. Enrichment analysis was performed to identify DEPs involved in KEGG pathways pertinent to biochemical metabolism and signal transduction. Furthermore, potential protein-protein interactions were predicted using the STRING database (http://string-db.org/)."],"omics_type":["Proteomics"],"labhead":["Yimin Chen"],"instrument_platform":[""],"labhead_affiliation":["Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Hangzhou, China"],"submission_type":["PARTIAL"],"species":["Homo Sapiens (human)"],"submitter_mail":["ymjy296@163.com"],"publication":["Not available"],"submitter_affiliation":["ymjy296@163.com"],"submitter_country":["China"],"additional_accession":[]},"is_claimable":false,"name":"Serum proteomics and metabolomics reveal the  characteristics of the A1762T/G1764A mutations in conjunction with the G1896A mutation.","description":"Background and Objective: CHB is a complex heterogeneous disease with a high incidence and mortality rate. Especially, the mutant strains with A1762T/G1764A and G1896A mutations gradually gained survival advantages during the population evolution process. However, our current understanding of the potential pathogenic mechanism of the mutant strains is limited. Our goal is to use multi-omics analysis to elucidate the potential molecular mechanisms, develop biomarkers for assessing the severity of the disease, and explore potential therapeutic targets.  Methods: Based on the sequencing results of serum HBV DNA in the samples, we finally included 108 patients with chronic hepatitis B. According to the sequencing results, they were divided into groups A (wild strain, WT = 27), B (G1896A = 27), C (A1762T/G1764A = 27), and D (A1762T/G1764A + G1896A = 27). We conducted non-target metabolomics and proteomics analyses to investigate the changes in the metabolism of infected liver cells caused by different site mutations. We selected the A1762T/G1764A group and the A1762T/G1764A + G1896A group for comparative analysis with the WT group, aiming to gain a deeper understanding of the pathogenic mechanism of the dominant mutant strains.  Results: Compared with WT, the A1762T/G1764A group and the A1762T/G1764A + G1896A group identified 242 and 64 as well as 226 and 79 differentially expressed metabolites and proteins, respectively. Through ipath pathway analysis and KEGG pathway mapping analysis, we found that A1762T/G1764A and A1762T/G1764A + G1896A might aggravate liver injury by affecting base repair and increase lipid accumulation in liver cells by down-regulating cholesterol metabolism. In the A1762T/G1764A + G1896A group, four proteins, APOC2, APOA2, CETP, and ANGPTL4, coordinated their functions to inhibit lipid metabolism and aggravate lipid accumulation in liver cells.  Conclusion: A1762T/G1764A and G1896A mutations may affect base repair and aggravate liver cell damage, and at the same time, by down-regulating the cholesterol metabolism pathway, aggravate lipid accumulation in liver cells and accelerate disease progression.","dates":{"publication":"2026-04-14","submission":"2025-08-04"},"accession":"PXD066939","cross_references":{"TAXONOMY":["NEWT:108018","NEWT:377960","NEWT:1131","NEWT:190486","NEWT:2042546","NEWT:148942","NEWT:295546","NEWT:258594","NEWT:1126","NEWT:1129","NEWT:89187","NEWT:309807","NEWT:89184","NEWT:309800","NEWT:1323429","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:2315688","NEWT:44270","NEWT:592321","NEWT:1073882","NEWT:6819","NEWT:428386","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:32264","NEWT:10034","NEWT:661410","NEWT:488003","NEWT:224326","NEWT:376619","NEWT:3765","NEWT:2433","NEWT:3767","NEWT:433727","NEWT:135622","NEWT:672127","NEWT:656061","NEWT:37965","NEWT:656064","NEWT:3760","NEWT:36630","NEWT:381198","NEWT:418106","NEWT:10029","NEWT:913645","NEWT:641809","NEWT:44250","NEWT:317447","NEWT:5530","NEWT:868565","NEWT:135674","NEWT:1562698","NEWT:11308","NEWT:12637","NEWT:2164133","NEWT:1180","NEWT:2767846","NEWT:1343074","NEWT:314344","NEWT:108061","NEWT:224308","NEWT:49928","NEWT:160621","NEWT:110368","NEWT:1916073","NEWT:1310161","NEWT:1230383","NEWT:77133","NEWT:1310165","NEWT:114727","NEWT:5516","NEWT:498211","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:1410384","NEWT:1310173","NEWT:161934","NEWT:1148","NEWT:5508","NEWT:135666","NEWT:419481","NEWT:5507","NEWT:1140","NCBITaxon:2157","NEWT:2066563","NEWT:1143","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:709964","NEWT:3712","NEWT:3711","NEWT:3714","NEWT:65121","NEWT:3715","NEWT:2065263","NEWT:1549675","NEWT:177437","NEWT:9014","NEWT:10891","NEWT:118221","NEWT:34869","NEWT:226126","NEWT:1616117","NEWT:34865","NEWT:28174","NEWT:550537","NEWT:284812","NEWT:3701","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:1246791","NEWT:34875","NEWT:9005","NEWT:34871","NEWT:9006","NEWT:33548","NEWT:1883426","NEWT:657321","NEWT:1423687","NEWT:10886","NEWT:3708","NEWT:536231","NEWT:219813","NEWT:1301262","NEWT:2305479","NEWT:215451","NEWT:460519","NEWT:272843","NEWT:272844","NEWT:1348799","NEWT:55784","NEWT:485","NEWT:2499525","NEWT:467144","NEWT:142786","NEWT:2853422","NEWT:487","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:46835","NEWT:216778","NEWT:376686","NEWT:237610","EFO:0001352","NEWT:219809","NEWT:219808","NEWT:119562","NEWT:1883446","NEWT:1233435","NEWT:118223","NEWT:141469","NEWT:272831","NEWT:987059","NEWT:491","NEWT:460523","NEWT:2423","NEWT:85694","NEWT:85692","NEWT:911045","NEWT:3750","NEWT:291146","NEWT:233271","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:278161","NEWT:415978","NEWT:410289","NEWT:191701","NEWT:9054","NEWT:472","NEWT:29459","NEWT:476","NEWT:28128","NEWT:470","NEWT:41122","NEWT:1328300","NEWT:748693","NCBITaxon:50557","NEWT:3735","NEWT:29491","NEWT:911022","NEWT:446","NEWT:153481","NEWT:714485","NEWT:445","NEWT:2003758","NEWT:29486","NEWT:63366","NEWT:63367","NEWT:29488","NEWT:215402","NEWT:3726","NEWT:30455","NEWT:28141","NEWT:9030","NEWT:9031","NEWT:3728","NEWT:108931","NEWT:219799","NEWT:1325292","NEWT:219798","NEWT:548","NEWT:150475","NEWT:256737","NEWT:51350","NEWT:8694","NEWT:8692","NEWT:542","NEWT:394503","NEWT:13076","NEWT:219785","NEWT:451515","NEWT:8673","NEWT:550","NEWT:10804","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:42410","NEWT:1225786","NEWT:771870","NEWT:8665","NEWT:51338","NEWT:9995","NEWT:28112","NEWT:49012","NEWT:28110","NEWT:10832","NEWT:311339","NEWT:507601","NEWT:520","NEWT:64657","NEWT:186441","NEWT:2585209","NEWT:643680","NEWT:214092","NEWT:40697","NEWT:13095","NEWT:162425","NEWT:242124","NEWT:9986","NEWT:8654","NEWT:536","NEWT:8658","NEWT:1268063","NEWT:8657","NEWT:9983","NEWT:8655","NEWT:80833","NEWT:479096","NEWT:28108","NEWT:28104","NEWT:1114957","NEWT:568703","NEWT:568708","NEWT:52641","NEWT:353152","NEWT:116597","NEWT:353153","NEWT:116598","NEWT:227377","NEWT:1774284","NEWT:27689","NEWT:207769","NEWT:40674","NEWT:51329","NCBITaxon:1763","NEWT:443906","NEWT:13037","NEWT:519","NEWT:941638","NEWT:7394","NEWT:6063","NEWT:404330","NEWT:1328388","NEWT:13064","NEWT:300641","NEWT:39655","NEWT:38323","NEWT:206411","NEWT:80869","NEWT:214053","NEWT:80863","NEWT:665890","NEWT:52639","NEWT:52638","NEWT:8697","NEWT:861109","NEWT:8695","NEWT:1196866","NEWT:6039","NEWT:1045775","NEWT:1123869","NCBITaxon:1335626","NEWT:7370","NEWT:280406","NEWT:83906","NEWT:99488","NEWT:99487","NEWT:1134506","NEWT:255470","NEWT:762903","NEWT:27697","NEWT:86185","NEWT:9935","NEWT:266940","NEWT:287889","NEWT:9938","NEWT:1028307","NEWT:52603","NEWT:92867","NEWT:92866","NEWT:1344414","NEWT:202950","NEWT:741158","NEWT:1293091","NEWT:202956","NEWT:483179","NEWT:315750","NEWT:99490","NEWT:632957","NEWT:11294","NEWT:9925","NCBITaxon:9606","NEWT:1436183","NEWT:1479235","NEWT:4232","NEWT:9922","NEWT:416348","NEWT:105812","NEWT:11298","NEWT:4233","NEWT:4236","NEWT:398031","NEWT:196627","NEWT:523840","NEWT:487521","NEWT:1076878","NEWT:200308","NEWT:200302","NEWT:9913","NEWT:9915","NEWT:105841","NEWT:1170227","NEWT:2666255","NEWT:999810","NEWT:28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