Design of a Targeted Sequencing Assay to Detect Rare Mutations in Circulating Tumor DNA

Chen, Jianxia; He, Fusheng; Huang, Yiqiong; Lu, Shan; Fan, Haibo; Wang, Mingbang; Xu, Ruirong

doi:10.1089/gtmb.2018.0173

Cited by 5 publications

(3 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RPS6KA2, CYYR1, KDR, and GIMAP6 were discovered to be most correlated with the prognostic-related module eigengene, which was also found relevant to blood vessel development and cell proliferation in existing researches. For instance, KDR has been reported to acts as an important mediator of VEGF-induced endothelial proliferation, tubular morphogenesis and sprouting and associate with signaling by GPCR pathway ( 49 , 50 ). RPS6KA2 has been found to act downstream of EGFR, RAS, and ERK signaling, which mediates mitogenic and stress-induced activation of transcription factors and thus regulate the proliferation and differentiation of cells ( 51 , 52 ).…”

Section: Discussionmentioning

confidence: 99%

Exploration of an Integrative Prognostic Model of Radiogenomics Features With Underlying Gene Expression Patterns in Clear Cell Renal Cell Carcinoma

et al. 2021

View full text Add to dashboard Cite

BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most common malignancies in urinary system, and radiomics has been adopted in tumor staging and prognostic evaluation in renal carcinomas. This study aimed to integrate image features of contrast-enhanced CT and underlying genomics features to predict the overall survival (OS) of ccRCC patients.MethodWe extracted 107 radiomics features out of 205 patients with available CT images obtained from TCIA database and corresponding clinical and genetic information from TCGA database. LASSO-COX and SVM-RFE were employed independently as machine-learning algorithms to select prognosis-related imaging features (PRIF). Afterwards, we identified prognosis-related gene signature through WGCNA. The random forest (RF) algorithm was then applied to integrate PRIF and the genes into a combined imaging-genomics prognostic factors (IGPF) model. Furthermore, we constructed a nomogram incorporating IGPF and clinical predictors as the integrative prognostic model for ccRCC patients.ResultsA total of four PRIF and four genes were identified as IGPF and were represented by corresponding risk score in RF model. The integrative IGPF model presented a better prediction performance than the PRIF model alone (average AUCs for 1-, 3-, and 5-year were 0.814 vs. 0.837, 0.74 vs. 0.806, and 0.689 vs. 0.751 in test set). Clinical characteristics including gender, TNM stage and IGPF were independent risk factors. The nomogram integrating clinical predictors and IGPF provided the best net benefit among the three models.ConclusionIn this study we established an integrative prognosis-related nomogram model incorporating imaging-genomic features and clinical indicators. The results indicated that IGPF may contribute to a comprehensive prognosis assessment for ccRCC patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Exploration of an Integrative Prognostic Model of Radiogenomics Features With Underlying Gene Expression Patterns in Clear Cell Renal Cell Carcinoma

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The panel, which targeted the coding region of 404 immune-response molecule genes, included genes related to cytokines, receptors, innate immunity, and adaptive immunity and was designed in our previous study [ 52 ]; target region sequencing of the 404 immune-response genes was performed according to our published studies [ 54 , 55 ]. In brief, the small-fragment library was mixed with a hybridization block (iGeneTech, Beijing, China).…”

Section: Methodsmentioning

confidence: 99%

Identifying Rare Genetic Variants of Immune Mediators as Risk Factors for Autism Spectrum Disorder

Cai

Zhen²,

Liu

et al. 2022

Genes

Self Cite

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) affects more than 1% of children, and there is no viable pharmacotherapeutic agent to treat the core symptoms of ASD. Studies have shown that children with ASD show changes in their levels of immune response molecules. Our previous studies have shown that ASD is more common in children with folate receptor autoantibodies. We also found that children with ASD have abnormal gut immune function, which was characterized by a significant increase in the content of immunoglobulin A and an increase in gut-microbiota-associated epitope diversity. These studies suggest that the immune mechanism plays an important role in the occurrence of ASD. The present study aims to systematically assess gene mutations in immune mediators in patients with ASD. We collected genetic samples from 72 children with ASD (2–12 years old) and 107 healthy controls without ASD (20–78 years old). We used our previously-designed immune gene panel, which can capture cytokine and receptor genes, the coding regions of MHC genes, and genes of innate immunity. Target region sequencing (500×) and bioinformatics analytical methods were used to identify variants in immune response genes associated with patients with ASD. A total of 4 rare variants were found to be associated with ASD, including HLA-B: p.A93G, HLA-DQB1: p.S229N, LILRB2: p.R322H, and LILRB2: c.956-4C>T. These variants were present in 44.44% (32/72) of the ASD patients and were detected in 3.74% (4/107) of the healthy controls. We expect these genetic variants will serve as new targets for the clinical genetic assessment of ASD, and our findings suggest that immune abnormalities in children with ASD may have a genetic basis.

show abstract

“…Multiple factors such as cancer type, tumor stage, temporal and spatial heterogeneity of tumor, and different sampling time between tissue and plasma can cause differences. Due to the low content of ctDNA in plasma, it is significant to explore the lower detection limit [27]. Considering the impact of biological property and nonbiological factors above, it is more objective and recommended to verify the detectability near the detection limit by incorporating cell lines or artificially constructing standardized samples [28].…”

Section: Advantages and Disadvantages Of Ctdna As 5hmc Research Samplementioning

confidence: 99%

Hydroxymethylation and tumors: can 5-hydroxymethylation be used as a marker for tumor diagnosis and treatment?

Gao

2020

Hum Genomics

View full text Add to dashboard Cite

5-Methylcytosine (5mC) is considered as a common epigenetic modification that plays an important role in the regulation of gene expression. At the same time, 5-hydroxymethylcytosine (5hmC) has been found as an emerging modification of cytosine bases of recent years. Unlike 5mC, global 5hmC levels vary from tissues that have differential distribution both in mammalian tissues and in the genome. DNA hydroxymethylation is the process that 5mC oxidates into 5hmC with the catalysis of TET (ten-eleven translocation) enzymes. It is an essential option of DNA demethylation, which modulates gene expression by adjusting the DNA methylation level. Various factors can regulate the demethylation of DNA, such as environmental toxins and mental stress. In this review, we summarize the progress in the formation of 5hmC, and obtaining 5hmC in a cell-free DNA sample presents multiple advantages and challenges for the subject. Furthermore, the clinical potential for 5hmC modification in dealing with cancer early diagnosis, prognostic evaluation, and prediction of therapeutic effect is also mentioned.

show abstract

Design of a Targeted Sequencing Assay to Detect Rare Mutations in Circulating Tumor DNA

Cited by 5 publications

References 30 publications

Exploration of an Integrative Prognostic Model of Radiogenomics Features With Underlying Gene Expression Patterns in Clear Cell Renal Cell Carcinoma

Exploration of an Integrative Prognostic Model of Radiogenomics Features With Underlying Gene Expression Patterns in Clear Cell Renal Cell Carcinoma

Identifying Rare Genetic Variants of Immune Mediators as Risk Factors for Autism Spectrum Disorder

Hydroxymethylation and tumors: can 5-hydroxymethylation be used as a marker for tumor diagnosis and treatment?

Contact Info

Product

Resources

About