We present a new de novo transcriptome assembler, Bridger, which takes advantage of techniques employed in Cufflinks to overcome limitations of the existing de novo assemblers. When tested on dog, human, and mouse RNA-seq data, Bridger assembled more full-length reference transcripts while reporting considerably fewer candidate transcripts, hence greatly reducing false positive transcripts in comparison with the state-of-the-art assemblers. It runs substantially faster and requires much less memory space than most assemblers. More interestingly, Bridger reaches a comparable level of sensitivity and accuracy with Cufflinks. Bridger is available at https://sourceforge.net/projects/rnaseqassembly/files/?source=navbar.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0596-2) contains supplementary material, which is available to authorized users.

Biclustering extends the traditional clustering techniques by attempting to find (all) subgroups of genes with similar expression patterns under to-be-identified subsets of experimental conditions when applied to gene expression data. Still the real power of this clustering strategy is yet to be fully realized due to the lack of effective and efficient algorithms for reliably solving the general biclustering problem. We report a QUalitative BIClustering algorithm (QUBIC) that can solve the biclustering problem in a more general form, compared to existing algorithms, through employing a combination of qualitative (or semi-quantitative) measures of gene expression data and a combinatorial optimization technique. One key unique feature of the QUBIC algorithm is that it can identify all statistically significant biclusters including biclusters with the so-called ‘scaling patterns’, a problem considered to be rather challenging; another key unique feature is that the algorithm solves such general biclustering problems very efficiently, capable of solving biclustering problems with tens of thousands of genes under up to thousands of conditions in a few minutes of the CPU time on a desktop computer. We have demonstrated a considerably improved biclustering performance by our algorithm compared to the existing algorithms on various benchmark sets and data sets of our own. QUBIC was written in ANSI C and tested using GCC (version 4.1.2) on Linux. Its source code is available at: http://csbl.bmb.uga.edu/∼maqin/bicluster. A server version of QUBIC is also available upon request.

Background This retrospective review examines demographic/clinical characteristics and overall survival of patients with squamous cell carcinoma of the oropharynx (SCCOP) at a tertiary cancer center and reports the characteristics influencing any observed survival trends over time. Methods The study included 3891 newly diagnosed, previously untreated patients presenting to our institution between 1955 and 2004. Results Over time, patients presented at younger ages and were more likely to have base of tongue or tonsil tumors and to be never or former smokers. Patients diagnosed in 1995–2004 were almost half as likely to die as those diagnosed before 1995 (HR,0.6; 95% CI,0.6–0.8). In both multivariable and recursive partitioning survival analyses, the TNM staging system predicted survival of patients treated before 1995 but not of patients treated in 1995–2004. Conclusion Survival among patients with SCCOP improved substantially over the past 50 years. The main contributing factors were changes in clinical characteristics, in particular surrogates for HPV positivity. The current TNM staging system for SCCOP is inadequate. Incorporation of HPV status and perhaps smoking status is encouraged.

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Background:The characteristics, significance and potential cause of positive SARS-CoV-2 diagnoses in recovered coronavirus disease 2019 (COVID-19) patients post discharge (re-detectable positive, RP) remained elusive.Methods: A total of 262 COVID-19 patients discharged from January 23 to February 25, 2020 were enrolled into this study. RP and non-RP (NRP) patients were grouped according to disease severity, and the characterization at re-admission was analyzed. SARS-CoV-2 RNA and plasma antibody levels were measured, and all patients were followed up for at least 14 days, with a cutoff date of March 10, 2020.Results: A total of 14.5% of RP patients were detected. These patients were characterized as young and displayed mild and moderate conditions compared to NRP patients while no severe patients were RP. RP patients displayed fewer symptoms but similar plasma antibody levels during their hospitalization compared to NRP patients. Upon hospital readmission, these patients showed no obvious symptoms or disease progression. All 21 close contacts of RP patients were tested negative for viral RNA and showed no suspicious symptoms. Eighteen out of 24 of RNA-negative samples detected by the commercial kit were tested positive for viral RNA using a hyper-sensitive method, suggesting that these patients were potential carriers of the virus after recovery from COVID-19.Conclusions: Our results indicated that young patients, with a mild diagnosis of COVID-19 are more likely to display RP status after discharge. These patients show no obvious symptoms or disease progression upon re-admission. More sensitive RNA detection methods are required to monitor these patients. Our findings provide information and evidence for the management of convalescent COVID-19 patients.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) may alter the processing, transcription, and expression of miRNAs and, thus, may contribute to cancer development. The authors hypothesized that common polymorphisms in pre-miRNAs are associated individually and (more likely) collectively with the risk of squamous cell carcinoma of the head and neck (SCCHN). METHODS: The authors genotyped 4 common polymorphisms in pre-miRNAs: Homo sapiens miRNA 146a (hsa-mir-146a) (reference SNP 2910164 [rs2910164]; guanine to cytosine [G!C]), hsa-mir-149 (rs2292832; guanine to thymine [G!T]), hsa-mir-196a2 (rs11614913; C!T), and hsa-mir-499 (rs3746444; adenine to guanine [A!G]) in 1109 patients with SCCHN (cases) and in 1130 cancer-free patients (controls) in a non-Hispanic white population that was frequency-matched by age and sex. Univariate and multivariate logistic regression models were used to calculate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the 4 SNPs that were studied, the hsa-mir-499 AG and GG genotypes were associated with a reduced risk of SCCHN (OR, 0.83; 95% CI, 0.69-0.99). When the 4 SNPs were combined according to putative risk genotype, the number of observed risk genotypes was associated with an increased risk of SCCHN in a doseresponse manner with ORs of 1.0, 1.20, and 1.40 for individuals who had 0 or 1 risk genotypes, 2 or 3 risk genotypes, and 4 risk genotypes, respectively (P trend ¼ .037). Specifically, the risk was 1.23-fold (95% CI, 0.98-fold to 1.56-fold) for individuals with 2 to 4 risk genotypes and 1.40-fold (95% CI, 1.02-fold to 1.92-fold) for individuals who had 4 risk genotypes compared with individuals who had 0 or 1 risk genotypes. This risk was more pronounced in men and in patients with oropharyngeal cancer. CONCLUSIONS: The combined risk genotypes of 4 common SNPs in pre-miRNAs were associated significantly with a moderately increased risk of SCCHN. Larger studies are needed to validate the current findings. Cancer 2010;116:4753-60.

Transcription factors of the NAC family are known to be involved in various growth or developmental processes and in regulation of response to environmental stresses. In the present study, we report that Arabidopsis ATAF1 is a negative regulator of defense responses against both necrotrophic fungal and bacterial pathogens. Expression of ATAF1 was downregulated after infection with Botrytis cinerea or Pseudomonas syringae pv. tomato or after treatment with salicylic acid (SA), jasmonic acid, and 1-amino cyclopropane-1-carboxylic acid (the precursor of ethylene biosynthesis). Transgenic plants that overexpress the ATAF1 gene (ATAF1-OE) showed increased susceptibility while expression of an ATAF1 chimeric repressor construct (ATAF1-SRDX) exhibited enhanced resistance to P. syringae pv. tomato DC3000, B. cinerea, and Alternaria brassicicola. The ataf1 mutant plants showed no significant resistance against the pathogens tested. After inoculation with B. cinerea or P. syringae pv. tomato DC3000, expressions of defense-related genes PR-1, PR-5. and PDF1.2 were upregulated in the ATAF1-SRDX plants but attenuated or unchanged in the ATAF1-OE plants. In ATAF1-OE plants, SA-induced expression of pathogenesis-related genes and disease resistance against P. syringae pv. tomato DC3000 was partially suppressed. Increased levels of reactive oxygen species (i.e., H(2)O(2) and superoxide anion) accumulated only in the ATAF1-OE but not in the ATAF1-SRDX plants after Botrytis spp. infection. Our studies provide direct genetic evidence for the role of ATAF1 as a negative regulator of defense response against different type of pathogens.

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