Weimin Ci

Beijing Institute of Genomics

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i-10 index

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Yue Shi

Heilongjiang University

Liqun Zhou

Peking University First Hospital

Ari Melnick

Cornell University

Leandro Cerchietti

Cornell University

Olivier Elemento

Lander Institute

Shao Ning Yang

Cornell University

Philmo Oh

New York University

Katerina Hatzi

Cornell University

Ivan Maillard

University of Pennsylvania

Camille W. Graham

Prisma Health

Cooperative Institutions

Chinese Academy of Sciences

155

Peking University

125

University of Chinese Academy of Sciences

108

Chinese Academy of Medical Sciences & Peking Union Medical College

Peking University First Hospital

Capital Medical University

Sun Yat-sen University

Beijing Institute of Genomics

Sichuan University

Wuhan University

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Distal regulatory elements identified by methylation and hydroxymethylation haplotype blocks from mouse brain

Epigenetics & Chromatin (2018)

Qin Ma Zhengzheng Xu Huan Lü Ziying Xu Yuanyuan Zhou

5-Hydroxymethylcytosine (5hmC) is an oxidation product of 5-methylcytosine (5mC), and adjacent CpG sites in mammalian genome can be co-methylated and co-hydroxymethylated due to the processivity of DNMT and TET enzymes. We applied TAB-seq and oxBS-seq to selectively detect 5hmC and 5mC at base resolution in the mouse cortex, olfactory bulb and cerebellum tissues. We found that majority of the called 5hmC CpG sites frequently have 5mC modification simultaneously and are enriched in gene body regions of neuron development-related genes in brain tissues. Strikingly, by a systematic search of regions that show highly coordinated methylation and hydroxymethylation (MHBs and hMHBs), we found that MHBs significantly overlapped with hMHBs in gene body regions. Moreover, using a metric called methylation haplotype load, we defined a subset of 1361 tissue-specific MHBs and 3818 shared MHBs. Shared MHBs with low MHL correspond with developmental enhancers, and tissue-specific MHBs resemble the regulatory elements for tissue identity. Our results provide new insights into the role of coordinately oxidized 5mC to 5hmC as distal regulatory elements may involve in regulating tissue identity.

CpG site

5-Methylcytosine

10.1186/s13072-018-0248-3

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Citations (7)

Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation

Journal of Experimental & Clinical Cancer Research (2015)

Lei Zhang Gengyan Xiong Dong Fang Xuesong Li Jin Liu

Aberrant methylation of genes is one of the most common epigenetic modifications involved in the development of urothelial carcinoma. However, it is unknown the predictive role of methylation to contralateral new upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We retrospectively investigated the predictive role of DNA methylation and other clinicopathological factors in the contralateral upper tract urothelial carcinoma (UTUC) recurrence after radical nephroureterectomy (RNU) in a large single-center cohort of patients.In a retrospective design, methylation of 10 genes was analyzed on tumor specimens belonging to 664 consecutive patients treated by RNU for primary UTUC. Median follow-up was 48 mo (range: 3-144 mo). Gene methylation was accessed by methylation-sensitive polymerase chain reaction, and we calculated the methylation index (MI), a reflection of the extent of methylation. The log-rank test and Cox regression were used to identify the predictor of contralateral UTUC recurrence.Thirty (4.5%) patients developed a subsequent contralateral UTUC after a median follow-up time of 27.5 (range: 2-139) months. Promoter methylation for at least one gene promoter locus was present in 88.9% of UTUC. Fewer methylation and lower MI (P = 0.001) were seen in the tumors with contralateral UTUC recurrence than the tumors without contralateral recurrence. High MI (P = 0.007) was significantly correlated with poor cancer-specific survival. Multivariate analysis indicated that unmethylated RASSF1A (P = 0.039), lack of bladder recurrence prior to contralateral UTUC (P = 0.009), history of renal transplantation (P < 0.001), and preoperative renal insufficiency (P = 0.002) are independent risk factors for contralateral UTUC recurrence after RNU.Our data suggest a potential role of DNA methylation in predicting contralateral UTUC recurrence after RNU. Such information could help identify patients at high risk of new contralateral UTUC recurrence after RNU who need close surveillance during follow up.

10.1186/s13046-015-0120-2

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Citations (15)

Biomarkers of aging

Science China Life Sciences (2023)

Hainan Bao Jiani Cao Mengting Chen Chen Min Wei Chen

Biological age

Cellular Aging

Healthy aging

Cellular senescence

10.1007/s11427-023-2305-0

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Citations (178)

Sensitive Determination of Onco-metabolites of D- and L-2-hydroxyglutarate Enantiomers by Chiral Derivatization Combined with Liquid Chromatography/Mass Spectrometry Analysis

Scientific Reports (2015)

Qing-Yun Cheng Jun Xiong Wei Huang Qin Ma Weimin Ci

Abstract 2-hydroxyglutarate (2HG) is a potent competitor of α-ketoglutarate (α-KG) and can inhibit multiple α-KG dependent dioxygenases that function on the epigenetic modifications. The accumulation of 2HG contributes to elevated risk of malignant tumors. 2HG carries an asymmetric carbon atom in its carbon backbone and differentiation between D-2-hydroxyglutarate (D-2HG) and L-2-hydroxyglutarate (L-2HG) is crucially important for accurate diagnosis of 2HG related diseases. Here we developed a strategy by chiral derivatization combined with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis for highly sensitive determination of D-2HG and L-2HG enantiomers. N -(p-toluenesulfonyl)-L-phenylalanyl chloride (TSPC) was used to derivatize 2HG. The formed diastereomers by TSPC labeling can efficiently improve the chromatographic separation of D-2HG and L-2HG. And derivatization by TSPC could also markedly increase the detection sensitivities by 291 and 346 folds for D-2HG and L-2HG, respectively. Using the developed method, we measured the contents of D-2HG and L-2HG in clear cell renal cell carcinoma (ccRCC) tissues. We observed 12.9 and 29.8 folds increase of D-2HG and L-2HG, respectively, in human ccRCC tissues compared to adjacent normal tissues. The developed chiral derivatization combined with LC-ESI-MS/MS analysis offers sensitive determination of D-2HG and L-2HG enantiomers, which benefits the precise diagnosis of 2HG related metabolic diseases.

Diastereomer

10.1038/srep15217

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Citations (73)

The copy number variation signatures in upper tract urothelial carcinoma define distinct subtypes with prognostic relevance

European Urology Open Science (2020)

Guolian Bao Huan Lü Yanping Liang Zhaomin Xu Yun Shi

Clinical Significance

Relevance

Variation (astronomy)

10.1016/s2666-1683(20)34089-1

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Citations (0)

Additional file 6 of Decoding the multicellular ecosystem of vena caval tumor thrombus in clear cell renal cell carcinoma by single-cell RNA sequencing

Figshare (2022)

Yue Shi Qi Zhang Hai Bi Min Lu Yezhen Tan

Additional file 6: Table S5. Differential expression results for all endothelial clusters and all myofibroblast clusters, and published gene signatures for GSEA, related to Fig. 5.

Multicellular organism

10.6084/m9.figshare.19498231

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Citations (0)

UCseek: ultrasensitive early detection and recurrence monitoring of urothelial carcinoma by shallow-depth genome-wide bisulfite sequencing of urinary sediment DNA

EBioMedicine (2023)

Ping Wang Yue Shi Jianye Zhang Jianzhong Shou Mingxin Zhang

Bisulfite sequencing

10.1016/j.ebiom.2023.104437

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Citations (5)

Urothelial Carcinoma Detection Based on Copy Number Profiles of Urinary Cell-Free DNA by Shallow Whole-Genome Sequencing

Clinical Chemistry (2019)

Guangzhe Ge Peng Ding Bao Guan Yuanyuan Zhou Yanqing Gong

Abstract BACKGROUND Current noninvasive assays for urothelial carcinoma (UC) lack clinical sensitivity and specificity. Given the utility of plasma cell-free DNA (cfDNA) biomarkers, the development of urinary cfDNA biomarkers may improve the diagnostic sensitivity. METHODS We assessed copy number alterations (CNAs) by shallow genome-wide sequencing of urinary cfDNA in 95 cancer-free individuals and 65 patients with UC, 58 with kidney cancer, and 45 with prostate cancer. We used a support vector machine to develop a diagnostic classifier based on CNA profiles to detect UC (UCdetector). The model was further validated in an independent cohort (52 patients). Genome sequencing data of tumor specimens from 90 upper tract urothelial cancers (UTUCs) and CNA data for 410 urothelial carcinomas of bladder (UCBs) from The Cancer Genome Atlas were used to validate the classifier. Genome sequencing data for urine sediment from 32 patients with UC were compared with cfDNA. To monitor the treatment efficacy, we collected cfDNA from 7 posttreatment patients. RESULTS Urinary cfDNA was a more sensitive alternative to urinary sediment. The UCdetector could detect UC at a median clinical sensitivity of 86.5% and specificity of 94.7%. UCdetector performed well in an independent validation data set. Notably, the CNA features selected by UCdetector were specific markers for both UTUC and UCB. Moreover, CNA changes in cfDNA were consistent with the treatment effects. Meanwhile, the same strategy could localize genitourinary cancers to tissue of origin in 70.1% of patients. CONCLUSIONS Our findings underscore the potential utility of urinary cfDNA CNA profiles as a basis for noninvasive UC detection and surveillance.

Cell-free fetal DNA

10.1373/clinchem.2019.309633

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Citations (38)

PCaseek: ultraspecific urinary tumor DNA detection using deep learning for prostate cancer diagnosis and Gleason grading

Cell Discovery (2024)

Gaojie Li Ye Wang Ying Wang Baojun Wang Yuan Liang

Grading (engineering)

10.1038/s41421-024-00710-y

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Citations (0)

MOESM3 of Distal regulatory elements identified by methylation and hydroxymethylation haplotype blocks from mouse brain