ABSTRACT
Methods for the de novo identification of microRNA (miRNA) have been developed using a range of sequence-based features. With the increasing availability of next generation sequencing (NGS) transcriptome data, there is a need for miRNA identification that integrates both NGS transcript expression-based patterns as well as advanced genomic sequence-based methods. While miRDeep2 does examine the predicted secondary structure of putative miRNA sequences, it does not leverage many of the sequence-based features used in state-of-the-art de novo methods. Meanwhile, other NGS-based methods, such as miRanalyzer, place an emphasis on sequence-based features without leveraging advanced expression-based features reflecting miRNA biosynthesis. This represents an opportunity to combine the strengths of NGS-based analysis with recent advances in de novo sequence-based miRNA prediction. We here develop a method, microRNA Prediction using Integrated Evidence (miPIE), which integrates both expression-based and sequence-based features to achieve significantly improved miRNA prediction performance. Feature selection identifies the 20 most discriminative features, 3 of which reflect strictly expression-based information. Evaluation using precision-recall curves, for six NGS data sets representing six diverse species, demonstrates substantial improvements in prediction performance compared to three methods: miRDeep2, miRanalyzer, and mirnovo. The individual contributions of expression-based and sequence-based features are also examined and we demonstrate that their combination is more effective than either alone.
Subject(s)
High-Throughput Nucleotide Sequencing/methods , MicroRNAs/metabolism , User-Computer Interface , Animals , Databases, Genetic , Humans , Sequence Analysis, RNASubject(s)
Adenocarcinoma/secondary , Breast Neoplasms/secondary , Liver Neoplasms/secondary , Pancreatic Neoplasms/pathology , Skin Neoplasms/secondary , Adenocarcinoma/pathology , Aged , Biopsy , Biopsy, Needle , Breast/pathology , Breast Neoplasms/pathology , Diagnosis, Differential , Fat Necrosis/pathology , Female , Humans , Liver Neoplasms/pathology , Necrosis , Pancreas/pathology , Panniculitis/pathology , Skin/pathology , Skin Neoplasms/pathologyABSTRACT
We describe a recent case of pulmonary hyalinizing granuloma presenting classically in a young black American female. The diagnosis was made by histopathologic examination. The etiology of this entity remains elusive, however, an abnormal response involving the immune system to an undefined agent (or agents) is the most likely explanation.
Subject(s)
Granuloma/pathology , Lung Diseases/pathology , Adult , Female , Granuloma/etiology , Humans , Lung Diseases/etiologyABSTRACT
Time-dependent effects of elevated PO2 upon hamster tracheal rings in culture were examined. Ciliary activity of rings in 0.20 and 0.40 O2 remained stable for 144 h. Ciliary activity decreased 25% following 120 h exposure to 0.60 O2 and 50% within 72 h exposure to 0.95 O2. Ciliostasis occurred by 144 h at 0.95 O2. [3H]Leucine uptake progressively decreased during 24 to 144 h exposure to 0.40, 0.60, and 0.95 O2 when compared to 0.20 O2. Tracheal explants incubated for 6 days under 0.20 and 0.40 O2 had intact epithelial surface with abundant cilia, and no mucus present (scanning electron microscopy). Explants incubated under 0.60 O2 contained mucus globules by 3 days. Incubation in 0.95 O2 resulted in mucus globules within 3 days and epithelial sloughing, loss of cilia, and increased mucus globules within 6 days. Time and O2 dependent increases in nuclear atypia, leukocytic infiltration into submucosal area, and focal flattening of pseudostratified ciliated epithelium were observed (light microscopy). These changes progressed following 6 days' exposure to 0.95 O2 to complete loss of normal epithelium, with broken-up, epithelial cells along the tracheal lumen.
