Has globalization strengthened South Korea's national research system?

노트 : The authors acknowledge a support from the SSK (Social Science Korea) Program funded by National Research Foundation of South Korea; NRF-2010-330-B00232

Mapping genomic regulation of kidney disease and traits through high-resolution and interpretable eQTLs

Expression quantitative trait locus (eQTL) studies illuminate genomic variants that regulate specific genes and contribute to fine-mapped loci discovered via genome-wide association studies (GWAS). Efforts to maximize their accuracy are ongoing. Using 240 glomerular (GLOM) and 311 tubulointerstitial (TUBE) micro-dissected samples from human kidney biopsies, we discovered 5371 GLOM and 9787 TUBE genes with at least one variant significantly associated with expression (eGene) by incorporating kidney single-nucleus open chromatin data and transcription start site distance as an integrative prior for Bayesian statistical fine-mapping. The use of an integrative prior resulted in higher resolution eQTLs illustrated by (1) smaller numbers of variants in credible sets with greater confidence, (2) increased enrichment of partitioned heritability for GWAS of two kidney traits, (3) an increased number of variants colocalized with the GWAS loci, and (4) enrichment of computationally predicted functional regulatory variants. A subset of variants and genes were validated experimentally in vitro and using a Drosophila nephrocyte model. More broadly, this study demonstrates that tissue-specific eQTL maps informed by single-nucleus open chromatin data have enhanced utility for diverse downstream analyses

An empirical study of the effect of background data size on the stability of SHapley Additive exPlanations (SHAP) for deep learning models

Nowadays, the interpretation of why a machine learning (ML) model makes certain inferences is as crucial as the accuracy of such inferences. Some ML models like the decision tree possess inherent interpretability that can be directly comprehended by humans. Others like artificial neural networks (ANN), however, rely on external methods to uncover the deduction mechanism. SHapley Additive exPlanations (SHAP) is one of such external methods, which requires a background dataset when interpreting ANNs. Generally, a background dataset consists of instances randomly sampled from the training dataset. However, the sampling size and its effect on SHAP remain to be unexplored. In our empirical study on the MIMIC-III dataset, we show that the two core explanations - SHAP values and variable rankings fluctuate when using different background datasets acquired from random sampling, indicating that users cannot unquestioningly trust the one-shot interpretation from SHAP. Luckily, such fluctuation decreases with the increase of the background dataset size. Also, we notice an U-shape in the stability assessment of SHAP variable rankings, demonstrating that SHAP is more reliable in ranking the most and least important variables compared to moderately important ones. Overall, our results suggest that users should take into account how background data affects SHAP results, with improved SHAP stability as the background sample size increases

Microbial liberation of N-methylserotonin from orange fiber in gnotobiotic mice and humans

Plant fibers in byproduct streams produced by non-harsh food processing methods represent biorepositories of diverse, naturally occurring, and physiologically active biomolecules. To demonstrate one approach for their characterization, mass spectrometry of intestinal contents from gnotobiotic mice, plus in vitro studies, revealed liberation of N-methylserotonin from orange fibers by human gut microbiota members including Bacteroides ovatus. Functional genomic analyses of B. ovatus strains grown under permissive and non-permissive N-methylserotonin mining conditions revealed polysaccharide utilization loci that target pectins whose expression correlate with strain-specific liberation of this compound. N-methylserotonin, orally administered to germ-free mice, reduced adiposity, altered liver glycogenesis, shortened gut transit time, and changed expression of genes that regulate circadian rhythm in the liver and colon. In human studies, dose-dependent, orange-fiber-specific fecal accumulation of N-methylserotonin positively correlated with levels of microbiome genes encoding enzymes that digest pectic glycans. Identifying this type of microbial mining activity has potential therapeutic implications

TRA-1-60-positive/CD45low cells found in the peripheral blood of prostate cancer patients with metastatic disease – A proof-of-concept study

Purpose Over 90% of all cancer related deaths are due to metastasis. However, current diagnostic tools can\u27t reliably discriminate between invasive and localized cancers. Patients and methods In this proof-of-concept study, we employed the embryonic stem cell marker TRA-1-60 (TRA+) to identify TRA + cells within the blood of prostate cancer patients and searched for TRA + cells in men with metastatic and localized cancers. We isolated whole peripheral blood mononuclear cells from 26 metastatic prostate cancer patients, from 13 patients with localized prostate cancer and from 17 healthy controls. Cells were stained for DAPI, CD45 and TRA + by immunofluorescence and imaged by epi-fluorescence microscopy. Imaged-based software was used both to identify TRA + cells, and to analyze CD45 levels in TRA+ and negative cells. Results We found high numbers of TRA + cells within the blood of metastatic cancer patients, whereas healthy individuals or men with localized prostate cancer showed none or very low numbers of TRA + cells. Further analysis of the CD45 levels of TRA + cells revealed a small population of TRA + cells with almost undetectable CD45 levels that were found frequently in metastatic prostate cancer patients. By excluding CD45 positive cells from the TRA + cell pool, we were able to refine the assay to be highly specific in identifying men with metastatic disease. In fact, the difference of CD45 levels between TRA+ and negative cells was a robust measure to distinguish between men with localized and metastatic prostate cancers in this small patient cohort. Conclusions The data suggest that metastatic prostate cancer patient have significant numbers of TRA+/CD45low cells which might represent a potential tool for diagnostic assessment in the future