Dataset Information

HLA predictions from the bronchoalveolar lavage fluid samples of five patients at the early stage of the wuhan seafood market COVID-19 outbreak.

ABSTRACT: We are in the midst of a global viral pandemic, one with no cure and a high mortality rate. The Human Leukocyte Antigen (HLA) gene complex plays a critical role in host immunity. We predicted HLA class I and II alleles from the transcriptome sequencing data prepared from the bronchoalveolar lavage fluid samples of five patients at the early stage of the COVID-19 outbreak. We identified the HLA-I allele A*24:02 in four out of five patients, which is higher than the expected frequency (17.2%) in the South Han Chinese population. The difference is statistically significant with a p-value less than 10^-4. Our analysis results may help provide future insights on disease susceptibility.

SUBMITTER: Warren RL

PROVIDER: S-EPMC7280900 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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HLA predictions from the bronchoalveolar lavage fluid samples of five patients at the early stage of the wuhan seafood market COVID-19 outbreak.

Warren René L RL Birol Inanç I

ArXiv 20200415

We are in the midst of a global viral pandemic, one with no cure and a high mortality rate. The Human Leukocyte Antigen (HLA) gene complex plays a critical role in host immunity. We predicted HLA class I and II alleles from the transcriptome sequencing data prepared from the bronchoalveolar lavage fluid samples of five patients at the early stage of the COVID-19 outbreak. We identified the HLA-I allele A*24:02 in four out of five patients, which is higher than the expected frequency (17.2%) in t ...[more]

PMID: 32550246

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Project description:BackgroundIt is now possible to comprehensively characterize the microbiota of the lungs using culture-independent, sequencing-based assays. Several sample types have been used to investigate the lung microbiota, each presenting specific challenges for preparation and analysis of microbial communities. Bronchoalveolar lavage fluid (BALF) enables the identification of microbiota specific to the lower lung but commonly has low bacterial density, increasing the risk of false-positive signal from contaminating DNA. The objectives of this study were to investigate the extent of contamination across a range of sample densities representative of BALF and identify features of contaminants that facilitate their removal from sequence data and aid in the interpretation of BALF sample 16S sequencing data.ResultsUsing three mock communities across a range of densities ranging from 8E+?02 to 8E+?09 16S copies/ml, we assessed taxonomic accuracy and precision by 16S rRNA gene sequencing and the proportion of reads arising from contaminants. Sequencing accuracy, precision, and the relative abundance of mock community members decreased with sample input density, with a significant drop-off below 8E+?05 16S copies/ml. Contaminant OTUs were commonly inversely correlated with sample input density or not reproduced between technical replicates. Removal of taxa with these features or physical concentration of samples prior to sequencing improved both sequencing accuracy and precision for samples between 8E+?04 and 8E+?06 16S copies/ml. For the lowest densities, below 8E+?03 16S copies/ml BALF, accuracy and precision could not be significantly improved using these approaches. Using clinical BALF samples across a large density range, we observed that OTUs with features of contaminants identified in mock communities were also evident in low-density BALF samples.ConclusionRelative abundance data and community composition generated by 16S sequencing of BALF samples across the range of density commonly observed in this sample type should be interpreted in the context of input sample density and may be improved by simple pre- and post-sequencing steps for densities above 8E+?04 16S copies/ml.

Project description:BackgroundThe pathogenesis of invasive aspergillosis (IA) is still unknown, but its progression is rapid and mortality rate remains high. Bronchoalveolar lavage fluid (BALF) galactomannan (GM) analysis has been used to diagnose IA. This study is aimed at making an accurate estimate of the whole accuracy of BALF-GM in diagnosing IA.MethodsAfter a systematic review of the study, a bivariate meta-analysis was used to summarize the specificity (SPE), the sensitivity (SEN), the positive likelihood ratios (PLR), and the negative likelihood ratios (NLR) of BALF-GM in diagnosing IA. The overall test performance was summarized using a layered summary receiver operating characteristic (SROC) curve. Subgroup analysis was performed to explore the heterogeneity between studies.ResultsA total of 65 studies that are in line with the inclusion criteria were included. The summary estimates of BALF-GM analysis are divided into four categories. The first is the proven+probable vs. possible+no IA, with an SPE, 0.87 (95% CI, 0.85-0.98); SEN, 0.81 (95% CI, 0.76-0.84); PLR, 9.78 (5.78-16.56); and NLR, 0.20 (0.14-0.29). The AUC was 0.94. The BALF-GM test for proven+probable vs. no IA showed SPE, 0.88 (95% CI, 0.87-0.90); SEN, 0.82 (95% CI, 0.78-0.85); PLR, 6.56 (4.93-8.75); and NLR, 0.24 (0.17-0.33). The AUC was 0.93. The BALF-GM test for proven+probable+possible vs. no IA showed SPE, 0.82 (95% CI, 0.79-0.95); SEN, 0.59 (95% CI, 0.55-0.63); PLR, 3.60 (2.07-6.25); and NLR, 0.31 (0.15-0.61). The AUC was 0.86. The analyses for others showed SPE, 0.85 (95% CI, 0.83-0.87); SEN, 0.89 (95% CI, 0.86-0.91); PLR, 6.91 (4.67-10.22); and NLR, 0.18 (0.13-0.26). The AUC was 0.94.ConclusionsThe findings of this BALF-GM test resulted in some impact on the diagnosis of IA. The BALF-GM assay is considered a method for diagnosing IA with high SEN and SPE. However, the patients' underlying diseases may affect the accuracy of diagnosis. When the cutoff is greater than 1, the sensitivity will be higher.

Dataset Information

HLA predictions from the bronchoalveolar lavage fluid samples of five patients at the early stage of the wuhan seafood market COVID-19 outbreak.

Publications

HLA predictions from the bronchoalveolar lavage fluid samples of five patients at the early stage of the wuhan seafood market COVID-19 outbreak.

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