Improved Measurements of RNA Structure Conservation with Generalized Centroid Estimators

Identification of non-protein-coding RNAs (ncRNAs) in genomes is a crucial task for not only molecular cell biology but also bioinformatics. Secondary structures of ncRNAs are employed as a key feature of ncRNA analysis since biological functions of ncRNAs are deeply related to their secondary structures. Although the minimum free energy (MFE) structure of an RNA sequence is regarded as the most stable structure, MFE alone could not be an appropriate measure for identifying ncRNAs since the free energy is heavily biased by the nucleotide composition. Therefore, instead of MFE itself, several alternative measures for identifying ncRNAs have been proposed such as the structure conservation index (SCI) and the base pair distance (BPD), both of which employ MFE structures. However, these measurements are unfortunately not suitable for identifying ncRNAs in some cases including the genome-wide search and incur high false discovery rate. In this study, we propose improved measurements based on SCI and BPD, applying generalized centroid estimators to incorporate the robustness against low quality multiple alignments. Our experiments show that our proposed methods achieve higher accuracy than the original SCI and BPD for not only human-curated structural alignments but also low quality alignments produced by CLUSTAL W. Furthermore, the centroid-based SCI on CLUSTAL W alignments is more accurate than or comparable with that of the original SCI on structural alignments generated with RAF, a high quality structural aligner, for which twofold expensive computational time is required on average. We conclude that our methods are more suitable for genome-wide alignments which are of low quality from the point of view on secondary structures than the original SCI and BPD

Balloon Enteroscopy-Assisted Endoscopic Retrograde Cholangiopancreatography for the Treatment of Common Bile Duct Stones in Patients with Roux-en-Y Gastrectomy: Outcomes and Factors Affecting Complete Stone Extraction

Background: Endoscopic retrograde cholangiopancreatography (ERCP) for extraction of common bile duct (CBD) stones in patients with Roux-en-Y gastrectomy (RYG) remains technically challenging. Methods: Seventy-nine RYG patients (median 79 years old) underwent short-type double-balloon enteroscopy-assisted ERCP (sDBE-ERCP) for CBD stones at three referral hospitals from 2011-2020. We retrospectively investigated the treatment outcomes and potential factors affecting complete stone extraction. Results: The initial success rates of reaching the papilla of Vater, biliary cannulation, and biliary intervention, including complete stone extraction or biliary stent placement, were 92%, 81%, and 78%, respectively. Of 57 patients with attempted stone extraction, complete stone extraction was successful in 74% for the first session and ultimately in 88%. The adverse events rate was 5%. The multivariate analysis indicated that the largest CBD diameter >= 14 mm (odds ratio (OR), 0.04; 95% confidence interval (CI), 0.01-0.58; p = 0.018) and retroflex position (OR, 6.43; 95% CI, 1.12-36.81; p = 0.037) were independent predictive factors affecting complete stone extraction achievement. Conclusions: Therapeutic sDBE-ERCP for CBD stones in a relatively elderly RYG cohort, was effective and safe. A larger CBD diameter negatively affected complete stone extraction, but using the retroflex position may be useful for achieving complete stone clearance

Protein-protein interactions of the hyperthermophilic archaeon Pyrococcus horikoshii OT3

BACKGROUND: Although 2,061 proteins of Pyrococcus horikoshii OT3, a hyperthermophilic archaeon, have been predicted from the recently completed genome sequence, the majority of proteins show no similarity to those from other organisms and are thus hypothetical proteins of unknown function. Because most proteins operate as parts of complexes to regulate biological processes, we systematically analyzed protein-protein interactions in Pyrococcus using the mammalian two-hybrid system to determine the function of the hypothetical proteins. RESULTS: We examined 960 soluble proteins from Pyrococcus and selected 107 interactions based on luciferase reporter activity, which was then evaluated using a computational approach to assess the reliability of the interactions. We also analyzed the expression of the assay samples by western blot, and a few interactions by in vitro pull-down assays. We identified 11 hetero-interactions that we considered to be located at the same operon, as observed in Helicobacter pylori. We annotated and classified proteins in the selected interactions according to their orthologous proteins. Many enzyme proteins showed self-interactions, similar to those seen in other organisms. CONCLUSION: We found 13 unannotated proteins that interacted with annotated proteins; this information is useful for predicting the functions of the hypothetical Pyrococcus proteins from the annotations of their interacting partners. Among the heterogeneous interactions, proteins were more likely to interact with proteins within the same ortholog class than with proteins of different classes. The analysis described here can provide global insights into the biological features of the protein-protein interactions in P. horikoshii

A Predictive Formula for Portal Venous Pressure Prior to Liver Resection Using Directly Measured Values

Purpose: Despite refinements in surgical techniques for liver resection, evaluation of hepatic reserve disparity remains one of the most common problems in liver surgery, especially for hepatic malignancies such as hepatocellular carcinoma (HCC). Portal venous pressure (PVP) is regarded one of the important factors in selecting treatment strategy, although its measurement can be invasive and complex. Methods: To establish a formula for calculating PVP preoperatively, intraoperative directly measured PVP was used in 177 patients with preoperative factors and liver function tests such as age, sex, virus status, platelet count, prothrombin time, albumin, total bilirubin, alanine aminotransferase (ALT), Child?Pugh grade, liver damage defined by the Liver Cancer Study Group of Japan, indocyanine green retention rate at 15 min (ICG-R15), and the aspartate transaminase (AST)-platelet ratio index (APRI). Results: Although 90% of the patients were classified as Child-Pugh A, median direct PVP was 16.5 cm H2O (5.5?37.0) and the percentage of PVP greater than 20 cm H2O was 27.1%, reflecting portal hypertension due to liver damage. After multiple regression analysis, the formula PVP (cmH2O) = EXP[2.606 + 0.01 × (ICG-R15) + 0.015 × APRI] was established from the measured data. Conclusion: Considering its simplicity of use, we have adopted this formula for predicting PVP in determining treatment strategy for HCC and other hepatic malignancies

Improving the accuracy of predicting secondary structure for aligned RNA sequences

Considerable attention has been focused on predicting the secondary structure for aligned RNA sequences since it is useful not only for improving the limiting accuracy of conventional secondary structure prediction but also for finding non-coding RNAs in genomic sequences. Although there exist many algorithms of predicting secondary structure for aligned RNA sequences, further improvement of the accuracy is still awaited. In this article, toward improving the accuracy, a theoretical classification of state-of-the-art algorithms of predicting secondary structure for aligned RNA sequences is presented. The classification is based on the viewpoint of maximum expected accuracy (MEA), which has been successfully applied in various problems in bioinformatics. The classification reveals several disadvantages of the current algorithms but we propose an improvement of a previously introduced algorithm (CentroidAlifold). Finally, computational experiments strongly support the theoretical classification and indicate that the improved CentroidAlifold substantially outperforms other algorithms