Biology subjects

Yoon, S.-S.

Publications and source records attributed to Yoon, S.-S..

7 recordsLinked to original sources

bioRxiv2024

Sequencing analysis of Helicobacter pylori infection in gastric mucosa and its progression to gastric mucosa-associated tissue (MALT) lymphoma

IntroductionThe pathogenesis of gastric mucosa-associated tissue (MALT) lymphoma is associated with Helicobacter pylori infection. Although treatment strategies and responsiveness according to the stage of gastric MALT lymphoma have been widely reported, a detailed study of the biological carcinogenic process is still required. MethodPaired, fresh tumor-adjacent normal and gastric mucosal tissue samples from 13 patients with gastric MALT lymphoma were prospectively collected. Whole exome sequencing (WES) and whole-transcriptome sequencing (WTS) data were generated. The analysis of mutations, gene fusion, gene expression, and the microbiome was stratified by H. pylori infection and disease status. ResultsSomatic mutations in TRAF3 and TNFAIP3 were identified in H. pylori-negative gastric MALT lymphoma. Fusions involving BIRC3-MALT1 (2 samples) and TBL1XR1-TP63 (1 sample with H. pylori infection) were detected. Stepwise comparative analysis of RNA expression revealed upregulation of immune response, inflammatory responses, and the NF- {kappa}B signaling pathway in H. pylori-positive MALT lymphoma cases. Pathways associated with pathogens were upregulated in H. pylori-negative MALT lymphoma cases, suggesting that infections other than H. pylori may affect lymphomagenesis. Microbiome analysis revealed that genus_Rothia was negatively correlated with alpha diversity. ConclusionA stepwise approach using diverse stages of WTS data revealed detailed pathogenic mechanisms of gastric MALT lymphoma. Chronic inflammation following infection contributes to gastric MALT lymphomagenesis in both H. pylori positive and negative cases.

bioinformatics↗

bioRxiv2023

Systematic analysis of disease-linked rare germline variants reveals new classes of cancer predisposing genes

Despite recent insights into cancer predisposition genes (CPGs), the contribution of rare germline variants to carcinogenesis remains unclear. Here, we examine the enrichment of rare germline variants in Mendelian disease-associated genes using PCAWG and the 1,000 Genomes Project. Using an integrative approach that considers disease classes, cellular pathways, and tissue expression profiles, we find that subsets of Online Mendelian Inheritance in Man (OMIM) genes are strong candidate CPGs. These genes were classified into five clusters suggesting diverse mechanisms underlie tumor progression. We further analyzed PAH gene which shows the strongest prevalence of rare germline variants in cancers (2.2%) compared to controls (0.7%). This enrichment was validated in two independent cancer cohorts and present the possibility of tumorigenesis by contributing immune-associated pathways. Our data argue that rare germline variants of Mendelian disease-associated genes contribute to cancer progression and suggest new CPG classifications that may underlie diverse tumorigenesis mechanisms.

bioinformatics↗

bioRxiv2021

Efficacy of double-stranded RNA for the large-scale control and prevention of sacbrood virus in Apis cerana (Hymenoptera: Apidae) apiaries

Sacbrood virus (SBV) infection in Apis cerana has caused tremendous damage in India, Thailand, Vietnam, and China since the 1970s. The disease caused by this virus results in colony collapse disorder in A. cerana and is also a devastating disease affecting A. cerana in South Korean apiaries. It has almost resulted in the elimination of the species. Therefore, control measures for this emerging threat are urgently needed. SBV RNA interference (RNAi) targeting VP1 was prepared to test the safety and efficacy of protection and treatment in artificially infected larvae and in infected colonies in South Korean apiaries. The efficacy of VP1 double-stranded RNA (dsRNA) was confirmed for the protection and treatment of infected larvae by increasing the survival rate in comparison with that in untreated larvae. Furthermore, an optimal application procedure was established for the large-scale RNAi treatment of SBV in apiaries. The protection of healthy colonies from SBV by RNAi was demonstrated in 100% of apiaries, and the treatment results showed that after five administrations, the SBV in infected colonies was mitigated to a safe level at which no symptoms of the disease were observed. Importantly, the low cost of dsRNA production in this study enables its application as a specific drug in large scale in South Korean apiculture.

microbiology↗

bioRxiv2020

Transcriptional analysis of immune modulatory genes in melanoma treated with PD-1 blockade

Abstract/SummaryWe aimed to characterize immunological features of melanoma patients treated with PD-1 blockade using tumor transcriptomic datasets. Response-dependent and response-independent predictors based on biological knowledge were investigated. Domain knowledge-driven regression-based analysis identified CEACAM1, CD40, B7-H3, and CD112 as key genes that determine the melanoma immune status. We devised the transcriptional deviance score (TDS) representing the individual sample-wise contribution to the immune network. The TDS not only showed good predictive power for immune checkpoint inhibitor (ICI) responses but also suggested specific gene interactions that determine ICI responses. Dynamic TDS changes following ICI treatment were related to long survival, indicating immune network modulation by ICIs occurred in responders. A predictive model incorporating B7-H3 and CEACAM1 expression, mutational status, clinical features, and the TDS showed excellent performance for ICI response. Thus, our approaches suggest a novel measure for the tumor immune temperature and provide insight into melanoma immunobiology. HighlightsO_LIWe applied outcome-independent and outcome-dependent methods to investigate melanoma immunobiology. C_LIO_LICEACAM1, CD40, B7-H3, and CD112 expression levels are key determinants of immune status. C_LIO_LIWe devised a TDS that could measure tumor immune network status at the individual level. C_LIO_LIIncorporating regression and correlation approaches greatly improves predictive power. C_LI

cancer biology↗

bioRxiv2020

Non-canonical immune response to the inhibition of DNA methylation via stabilization of endogenous retrovirus dsRNAs

5-Aza-2'-deoxycytidine, also known as decitabine, is a DNA-methyltransferase inhibitor (DNMTi) used to treat acute myeloid leukemia (AML). Decitabine activates the transcription of endogenous retroviruses (ERV), which can induce an immune response by acting as cellular double-stranded RNAs (dsRNAs). Here, we employ an image-based screening platform to identify dsRNA-binding factors that mediate the downstream effect of ERV induction. We find that Staufen1 (Stau1) knockdown decreases the interferon signature and rescues decitabine-mediated cell death. Moreover, Stau1 directly binds to ERV RNAs and stabilizes them, together with a long non-coding RNA TINCR. We further show that TINCR enhances the interaction between Stau1 and ERV RNAs. Analysis of a clinical patient cohort reveals that AML patients with low Stau1 and TINCR expressions exhibits inferior treatment outcomes to the DNMTi therapy. Our study reveals that decitabine-mediated cell death is a consequence of complex interactions among different dsRNA-binding proteins for access to their common dsRNA targets. HIGHLIHGTSO_LIImage-based RNAi screening reveals multiple dsRBPs regulate response to decitabine C_LIO_LIStau1 binds to ERV RNAs and affects their stability and subcellular localization C_LIO_LITINCR binds to Stau1 and enhances Stau1-ERV interactions C_LIO_LIAML/MDS patients with low Stau1 and TINCR expressions show poor response to DNMTis C_LI

molecular biology↗

bioRxiv2018

Oncogenic effects of germline mutations in lysosomal storage disease genes

Clinical observations have indicated that patients with Gaucher disease or Fabry disease are at increased risk of cancer. However, a systematic evaluation of the oncogenic effects of causal mutations of lysosomal storage diseases (LSDs) has been lacking. Here we report a comprehensive association analysis between potentially pathogenic germline mutations in LSD genes and cancer interrogating genomic (or exomic) variant datasets derived from the Pan-Cancer Analysis of Whole Genomes project (case cohort), the 1000 Genomes project (primary control cohort), and the Exome Aggregation Consortium that does not include The Cancer Genome Atlas subset (validation control cohort). We show that potentially pathogenic variants (PPVs) in 42 LSD genes are significantly enriched in cancer patients in a histology-dependent manner, cancer risk is higher in individuals with a greater number of PPVs, and cancer develops earlier in PPV carriers. Analysis of tumor genomic and transcriptomic data from the pancreatic adenocarcinoma cohort revealed potential mechanisms that might be involved in the oncogenic contribution of PPVs. Our findings extend the mechanistic understanding of inherited cancer susceptibility and highlight the promise of harnessing available therapeutic strategies to restore lysosomal function for personalized cancer prevention.

genetics↗

bioRxiv2018

Immuno-genomic PanCancer Landscape Reveals Diverse Immune Escape Mechanisms and Immuno-Editing Histories

Immune reactions in the tumor micro-environment are one of the cancer hallmarks and emerging immune therapies have been proven effective in many types of cancer. To investigate cancer genome-immune interactions and the role of immuno-editing or immune escape mechanisms in cancer development, we analyzed 2,834 whole genomes and RNA-seq datasets across 31 distinct tumor types from the PanCancer Analysis of Whole Genomes (PCAWG) project with respect to key immuno-genomic aspects. We show that selective copy number changes in immune-related genes could contribute to immune escape. Furthermore, we developed an index of the immuno-editing history of each tumor sample based on the information of mutations in exonic regions and pseudogenes. Our immuno-genomic analyses of pan-cancer analyses have the potential to identify a subset of tumors with immunogenicity and diverse background or intrinsic pathways associated with their immune status and immuno-editing history.

genomics↗