Seoul National University

About: Seoul National University is a education organization based out in Seoul, South Korea. It is known for research contribution in the topics: Population & Catalysis. The organization has 65879 authors who have published 138759 publications receiving 3715170 citations. The organization is also known as: SNU & Seoul-dae.

The transcriptional landscape and mutational profile of lung adenocarcinoma

Abstract: All cancers harbor molecular alterations in their genomes. The transcriptional consequences of these somatic mutations have not yet been comprehensively explored in lung cancer. Here we present the first large scale RNA sequencing study of lung adenocarcinoma, demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions, alternative splicing events, and expression outliers. Our results reveal the genetic basis of 200 lung adenocarcinomas in Koreans including deep characterization of 87 surgical specimens by transcriptome sequencing. We identified driver somatic mutations in cancer genes including EGFR, KRAS, NRAS, BRAF, PIK3CA, MET, and CTNNB1. Candidates for novel driver mutations were also identified in genes newly implicated in lung adenocarcinoma such as LMTK2, ARID1A, NOTCH2, and SMARCA4. We found 45 fusion genes, eight of which were chimeric tyrosine kinases involving ALK, RET, ROS1, FGFR2, AXL, and PDGFRA. Among 17 recurrent alternative splicing events, we identified exon 14 skipping in the proto-oncogene MET as highly likely to be a cancer driver. The number of somatic mutations and expression outliers varied markedly between individual cancers and was strongly correlated with smoking history of patients. We identified genomic blocks within which gene expression levels were consistently increased or decreased that could be explained by copy number alterations in samples. We also found an association between lymph node metastasis and somatic mutations in TP53. These findings broaden our understanding of lung adenocarcinoma and may also lead to new diagnostic and therapeutic approaches.

Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study

Abstract: PurposeCrizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non–small-cell lung cancer (NSCLC), but progression invariably occurs. We investigated the efficacy and safety of alectinib, a potent and selective ALK inhibitor with excellent CNS penetration, in patients with crizotinib-refractory ALK-positive NSCLC.Patients and MethodsAlectinib 600 mg was administered orally twice daily. The primary end point was objective response rate (ORR) by central independent review committee (IRC).ResultsOf the 138 patients treated, 84 patients (61%) had CNS metastases at baseline, and 122 were response evaluable (RE) by IRC. ORR by IRC was 50% (95% CI, 41% to 59%), and the median duration of response (DOR) was 11.2 months (95% CI, 9.6 months to not reached). In 96 patients (79%) previously treated with chemotherapy, the ORR was 45% (95% CI, 35% to 55%). Median IRC-assessed progression-free survival for all 138 patients was 8.9 months (95% CI, 5....

In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni.

Abstract: Several CRISPR-Cas9 orthologues have been used for genome editing. Here, we present the smallest Cas9 orthologue characterized to date, derived from Campylobacter jejuni (CjCas9), for efficient genome editing in vivo. After determining protospacer-adjacent motif (PAM) sequences and optimizing single-guide RNA (sgRNA) length, we package the CjCas9 gene, its sgRNA sequence, and a marker gene in an all-in-one adeno-associated virus (AAV) vector and produce the resulting virus at a high titer. CjCas9 is highly specific, cleaving only a limited number of sites in the human or mouse genome. CjCas9, delivered via AAV, induces targeted mutations at high frequencies in mouse muscle cells or retinal pigment epithelium (RPE) cells. Furthermore, CjCas9 targeted to the Vegfa or Hif1a gene in RPE cells reduces the size of laser-induced choroidal neovascularization, suggesting that in vivo genome editing with CjCas9 is a new option for the treatment of age-related macular degeneration.

Tropical Cyclones and Climate Change Assessment: Part II: Projected Response to Anthropogenic Warming

Abstract: Model projections of tropical cyclone (TC) activity response to anthropogenic warming in climate models are assessed. Observations, theory, and models, with increasing robustness, indicate ...

Internet traffic classification demystified: myths, caveats, and the best practices

Abstract: Recent research on Internet traffic classification algorithms has yield a flurry of proposed approaches for distinguishing types of traffic, but no systematic comparison of the various algorithms. This fragmented approach to traffic classification research leaves the operational community with no basis for consensus on what approach to use when, and how to interpret results. In this work we critically revisit traffic classification by conducting a thorough evaluation of three classification approaches, based on transport layer ports, host behavior, and flow features. A strength of our work is the broad range of data against which we test the three classification approaches: seven traces with payload collected in Japan, Korea, and the US. The diverse geographic locations, link characteristics and application traffic mix in these data allowed us to evaluate the approaches under a wide variety of conditions. We analyze the advantages and limitations of each approach, evaluate methods to overcome the limitations, and extract insights and recommendations for both the study and practical application of traffic classification. We make our software, classifiers, and data available for researchers interested in validating or extending this work.