| 1. |
- Zhang, Ruyang, et al.
(författare)
-
A Large-Scale Genome-Wide Gene-Gene Interaction Study of Lung Cancer Susceptibility in Europeans With a Trans-Ethnic Validation in Asians
- 2022
-
Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 17:8, s. 974-990
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Although genome-wide association studies have been conducted to investigate genetic variation of lung tumorigenesis, little is known about gene-gene (G × G) interactions that may influence the risk of non-small cell lung cancer (NSCLC).Methods: Leveraging a total of 445,221 European-descent participants from the International Lung Cancer Consortium OncoArray project, Transdisciplinary Research in Cancer of the Lung and UK Biobank, we performed a large-scale genome-wide G × G interaction study on European NSCLC risk by a series of analyses. First, we used BiForce to evaluate and rank more than 58 billion G × G interactions from 340,958 single-nucleotide polymorphisms (SNPs). Then, the top interactions were further tested by demographically adjusted logistic regression models. Finally, we used the selected interactions to build lung cancer screening models of NSCLC, separately, for never and ever smokers.Results: With the Bonferroni correction, we identified eight statistically significant pairs of SNPs, which predominantly appeared in the 6p21.32 and 5p15.33 regions (e.g., rs521828C6orf10 and rs204999PRRT1, ORinteraction = 1.17, p = 6.57 × 10−13; rs3135369BTNL2 and rs2858859HLA-DQA1, ORinteraction = 1.17, p = 2.43 × 10−13; rs2858859HLA-DQA1 and rs9275572HLA-DQA2, ORinteraction = 1.15, p = 2.84 × 10−13; rs2853668TERT and rs62329694CLPTM1L, ORinteraction = 0.73, p = 2.70 × 10−13). Notably, even with much genetic heterogeneity across ethnicities, three pairs of SNPs in the 6p21.32 region identified from the European-ancestry population remained significant among an Asian population from the Nanjing Medical University Global Screening Array project (rs521828C6orf10 and rs204999PRRT1, ORinteraction = 1.13, p = 0.008; rs3135369BTNL2 and rs2858859HLA-DQA1, ORinteraction = 1.11, p = 5.23 × 10−4; rs3135369BTNL2 and rs9271300HLA-DQA1, ORinteraction = 0.89, p = 0.006). The interaction-empowered polygenetic risk score that integrated classical polygenetic risk score and G × G information score was remarkable in lung cancer risk stratification.Conclusions: Important G × G interactions were identified and enriched in the 5p15.33 and 6p21.32 regions, which may enhance lung cancer screening models.
|
|
| 2. |
- Chen, Hongxia, et al.
(författare)
-
PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation
- 2024
-
Ingår i: Molecular Cancer Research. - 1541-7786. ; 22:1, s. 94-103
-
Tidskriftsartikel (refereegranskat)abstract
- Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells.
|
|
| 3. |
- Chen, Liangliang, et al.
(författare)
-
User-Friendly Genetic Conditional Knockout Strategies by CRISPR/Cas9
- 2018
-
Ingår i: STEM CELLS INTERNATIONAL. - : HINDAWI LTD. - 1687-966X .- 1687-9678.
-
Tidskriftsartikel (refereegranskat)abstract
- Loss-of-function studies are critically important in gene functional analysis of model organisms and cells. However, conditional gene inactivation in diploid cells is difficult to achieve, as it involves laborious vector construction, multifold electroporation, and complicated genotyping. Here, a strategy is presented for generating biallelic conditional gene and DNA regulatory region knockouts in mouse embryonic stem cells by codelivery of CRISPR-Cas9 and short-homology-arm targeting vectors sequentially or simultaneously. Collectively, a simple and rapid method was presented to knock out any DNA element conditionally. This approach will facilitate the functional studies of essential genes and regulatory regions during development.
|
|
| 4. |
- Glicksberg, Benjamin S., et al.
(författare)
-
Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits
- 2019
-
Ingår i: BMC Medical Genomics. - : BMC. - 1755-8794. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenetic loss-of-function variants (LoFs) associated with disease traits are increasingly recognized as critical evidence for the selection of therapeutic targets. We integrated the analysis of genetic and clinical data from 10,511 individuals in the Mount Sinai BioMe Biobank to identify genes with loss-of-function variants (LoFs) significantly associated with cardiovascular disease (CVD) traits, and used RNA-sequence data of seven metabolic and vascular tissues isolated from 600 CVD patients in the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study for validation. We also carried out in vitro functional studies of several candidate genes, and in vivo studies of one gene.ResultsWe identified LoFs in 433 genes significantly associated with at least one of 10 major CVD traits. Next, we used RNA-sequence data from the STARNET study to validate 115 of the 433 LoF harboring-genes in that their expression levels were concordantly associated with corresponding CVD traits. Together with the documented hepatic lipid-lowering gene, APOC3, the expression levels of six additional liver LoF-genes were positively associated with levels of plasma lipids in STARNET. Candidate LoF-genes were subjected to gene silencing in HepG2 cells with marked overall effects on cellular LDLR, levels of triglycerides and on secreted APOB100 and PCSK9. In addition, we identified novel LoFs in DGAT2 associated with lower plasma cholesterol and glucose levels in BioMe that were also confirmed in STARNET, and showed a selective DGAT2-inhibitor in C57BL/6 mice not only significantly lowered fasting glucose levels but also affected body weight.ConclusionIn sum, by integrating genetic and electronic medical record data, and leveraging one of the world's largest human RNA-sequence datasets (STARNET), we identified known and novel CVD-trait related genes that may serve as targets for CVD therapeutics and as such merit further investigation.
|
|
| 5. |
- Li, Yingzheng, et al.
(författare)
-
Influence of O-O formation pathways and charge transfer mediator on lipid bilayer membrane-like photoanodes for water oxidation
- 2024
-
Ingår i: Journal of Energy Chemistry. - : Elsevier. - 2095-4956 .- 2096-885X. ; 93, s. 526-537
-
Tidskriftsartikel (refereegranskat)abstract
- Inspired by the function of crucial components in photosystem II (PSII), electrochemical and dyesensitized photoelectrochemical (DSPEC) water oxidation devices were constructed by the selfassembly of well-designed amphipathic Ru(bda)-based catalysts (bda = 2,2'-bipyrdine-6,6'-dicarbonoxyl acid) and aliphatic chain decorated electrode surfaces, forming lipid bilayer membrane (LBM)-like structures. The Ru(bda) catalysts on electrode-supported LBM films demonstrated remarkable water oxidation performance with different O-O formation mechanisms. However, compared to the slow charge transfer process, the O-O formation pathways did not determine the PEC water oxidation efficiency of the dyesensitized photoanodes, and the different reaction rates for similar catalysts with different catalytic paths did not determine the PEC performance of the DSPECs. Instead, charge transfer plays a decisive role in the PEC water oxidation rate. When an indolo[3,2-b] carbazole derivative was introduced between the Ru (bda) catalysts and aliphatic chain-modified photosensitizer in LBM films, serving as a charge transfer mediator for the tyrosine-histidine pair in PSII, the PEC water oxidation performance of the corresponding photoanodes was dramatically enhanced.
|
|
| 6. |
- Qin, Na, et al.
(författare)
-
Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma
- 2021
-
Ingår i: Frontiers of Medicine. - : Springer-Verlag New York. - 2095-0217 .- 2095-0225. ; 15:2, s. 275-291
-
Tidskriftsartikel (refereegranskat)abstract
- Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95,P= 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
|
|
| 7. |
- Wang, Weixing, et al.
(författare)
-
Pavement crack image acquisition methods and crack extraction algorithms : A review
- 2019
-
Ingår i: Journal of Traffic and Transportation Engineering (English Edition). - : KEAI PUBLISHING LTD. - 2095-7564. ; 6:6, s. 535-556
-
Forskningsöversikt (refereegranskat)abstract
- The extraction of pavement cracks is always a hard task in image processing. In airport and road construction, cracking is the main factor for pavement damage, which can decrease the quality of pavement and affect transportation seriously. Cracks also exist in other artificial or natural objects, such as buildings, bridges, tunnels, etc. Among all the object images, pavement crack images are the most complex, so the image processing and analysis for them is harder than other crack images. From the early image acquisition based on photography technology to the current 3D laser scanning technology, the pavement crack image acquisition technology is becoming more convenient and efficient, but there are still challenges in the automatic processing and recognition of cracks in images. From the early global thresholding to deep learning algorithms, the research for crack extraction has been developed for about 40 years. There are many methods and algorithms that are satisfactory in pavement crack applications, but there is no standard until today. Therefore, in order to know the developing history and the advanced research, we have collected a number of literature in this research topic for summarizing the research artwork status, and giving a review of the pavement crack image acquisition methods and 2D crack extraction algorithms. Also, for image acquisition methods and pavement crack image segmentation, more detailed comparison and discussions are made.
|
|
| 8. |
- Wang, Yuzhuo, et al.
(författare)
-
Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls
- 2020
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:7, s. 1423-1429
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.Methods: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data from The Cancer Genome Atlas (TCGA) project.Results: We identified seven independent SNPs in five lung CDGs that were consistently associated with lung cancer risk in discovery (P < 0.001) and validation (P < 0.05) stages. Among these loci, rs78062588 in TPM3 (1q21.3) was a new lung cancer susceptibility locus (OR = 0.86, P = 1.65 x 10(-6)). Subgroup analysis by histologic types further identified nine lung CDGs. Analysis of somatic alterations found that in lung adenocarcinomas, rs78062588[C] allele (TPM3 in 1q21.3) was associated with elevated somatic copy number of TPM3 (OR = 1.16, P = 0.02). In lung adenocarcinomas, rs1611182 (HLA-A in 6p22.1) was associated with truncation mutations of the transcriptional misregulation in cancer pathway (OR = 0.66, P = 1.76 x 10(-3)).Conclusions: Genetic variants can regulate functions of lung CDGs and influence lung cancer susceptibility. Impact: Our findings might help unravel biological mechanisms underlying lung cancer susceptibility.
|
|
| 9. |
- Wei, S., et al.
(författare)
-
Historical trends of organic pollutants in sediment cores from Hong Kong
- 2008
-
Ingår i: Marine Pollution Bulletin. - : Elsevier. - 0025-326X .- 1879-3363. ; 57:6-12, s. 758-766
-
Tidskriftsartikel (refereegranskat)abstract
- Recent studies have indicated the occurrence of a wide range of trace organic contaminants, including polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in the Hong Kong environment. These contaminants are potentially harmful to ecological systems, particularly in coastal areas. In this study, two sediment cores (4 m) were collected from southern waters of Hong Kong in 2004 to study the historical trends, distribution patterns, and potential sources of trace organic contaminants. DDTs (p,p′-DDT, o,p′-DDT, p,p′-DDD, o,p′-DDD and p,p′-DDE), hexachlorohexanes (HCHs) (α and γ), hexachlorobenzene (HCB), and PCBs were detected in the samples, whereas other target compounds were all below detection limits. Many OCPs have not been produced or used for many years due to toxicological or environmental concerns and PCB use is prohibited in Hong Kong. However, some compounds were still detectable in recent years, and were found to be widely distributed in the environment, likely because of pollutant inputs from the highly industrialized Pearl River Delta region. These results provide important information on current and historical contamination in Hong Kong, and help to reconstruct the pollution history of these trace organic pollutants in Hong Kong coastal waters.
|
|
| 10. |
- YanHui, Fan, et al.
(författare)
-
The rates and patterns of insertions, deletions and substitutions in mouse and rat inferred from introns
- 2008
-
Ingår i: Chinese Science Bulletin. - : Elsevier BV. - 1001-6538 .- 1861-9541 .- 2095-9273 .- 2095-9281. ; 53:18, s. 2813-2819
-
Tidskriftsartikel (refereegranskat)abstract
- The rates and patterns of InDel (insertions and deletions) and substitution in rodent (mouse and rat) have been studied. The result reveals that deletions occur more frequently than insertions, and single nucleotide insertion and deletion are the most frequent in both mouse and rat. The frequencies of both deletions and insertions decrease rapidly with increasing InDels length, and the size distributions of both insertions and deletions can be described well by power-law. There are more AT-->G than GC-->AT substitutions in the introns of rat. However, there are more GC-->AT than AT-->GC substitutions in the introns in mouse. The deletion bias found in introns in mouse and rat supports the prediction that intron insertions are more deleterious than deletions because of reduced transcription and splicing efficiency. The patterns of substitution suggest that both composition and GC content are not equilibrium in the introns in rodents.
|
|
