JBrowse Jupyter: a Python interface to JBrowse 2.

MOTIVATION: JBrowse Jupyter is a package that aims to close the gap between Python programming and genomic visualization. Web-based genome browsers are routinely used for publishing and inspecting genome annotations. Historically they have been deployed at the end of bioinformatics pipelines, typically decoupled from the analysis itself. However, emerging technologies such as Jupyter notebooks enable a more rapid iterative cycle of development, analysis and visualization. RESULTS: We have developed a package that provides a Python interface to JBrowse 2's suite of embeddable components, including the primary Linear Genome View. The package enables users to quickly set up, launch and customize JBrowse views from Jupyter notebooks. In addition, users can share their data via Google's Colab notebooks, providing reproducible interactive views. AVAILABILITY AND IMPLEMENTATION: JBrowse Jupyter is released under the Apache License and is available for download on PyPI. Source code and demos are available on GitHub at https://github.com/GMOD/jbrowse-jupyter.

Randomized trial of gastric and colorectal endoscopic submucosal dissection defect closure comparing a novel through-the-scope suturing system with an over-the-scope suturing system (with video).

BACKGROUND AND AIMS: Mucosal closure adds time but reduces adverse events associated with endoscopic submucosal dissection (ESD). We aimed to assess the closure time (CT), technical success, and cost-effectiveness between a novel through-the-scope helix tack suture system (TTSS) and the over-the-scope suturing system (OTSS). METHODS: In this single-center, prospective, randomized trial, all patients undergoing ESD with anticipated closure were randomized 1:1 to TTSS (study group) or OTSS (control group). Primary outcomes were CT and overall CT (OCT; CT + setup time). Secondary outcomes were rates of technical success, adverse events, and cost-effectiveness. RESULTS: Forty patients were randomized to OTSS (n = 20) or TTSS (n = 20). OTSS and TTSS groups were similar with respect to age, gender, proportion of colorectal polyps, proximal colon polyps, and mean size of the resected specimen (40.9 mm vs 40.4 mm). The mean CT was 18.4 minutes for OTSS and 23.3 minutes for TTSS (P = .36). The mean OCT was 32 minutes for OTSS and 39.5 minutes for TTSS (P = .36). Closure with a primary device was successful in 17 cases (85%) with OTSS and 18 cases (90%) with TTSS (P = .63). No closure-related intraprocedural adverse events or delayed perforations were noted. Mean cost of closure was significantly lower in the TTSS group for lesions <35 mm (P = .008). CONCLUSIONS: TTSS was not found to be superior to OTSS with respect to CT and technical and clinical success for closure of gastric and colorectal ESD defects. TTSS is more cost-effective for closure of lesions <35 mm. (Clinical trial registration number: NCT04925271.).

Longitudinal outcomes of the endoscopic resection of nonpolypoid dysplastic lesions in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) are at risk of developing dysplasia. According to the Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations, "After complete removal of endoscopically resectable nonpolypoid dysplastic lesions, surveillance colonoscopy is suggested rather than colectomy." We sought to add data to the literature and hypothesized that the endoscopic resection of nonpolypoid colorectal dysplasia (NP-CRD) is safe and effective. METHODS: We conducted a retrospective study of a large cohort of patients with IBD at 2 medical centers who underwent colonoscopy between 2007 and 2018. Patients with at least 1 nonpolypoid lesion ≥10 mm were identified. We measured the feasibility of endoscopic resection, incidence of local recurrence, incidence of cancer, need for surgery, and frequency of adverse events. RESULTS: We studied 326 patients who underwent a mean ± standard deviation of 3.6 ± 3.0 (range, 1-16) colonoscopies during a total follow-up of 1208 patient-years. In 36 patients, 161 lesions ≥10 mm were identified, 63 of which were nonpolypoid (mean size, 17.8 ± 8.9 mm; range, 10-45 mm) (prevalence, 7.7%). The majority of nonpolypoid lesions (96.8% [61 of 63]) were managed endoscopically. Four lesions (mean index lesion size, 32.5 ±11.0 mm) had small local recurrences that were successfully retreated with endoscopy. There were no severe adverse events related to IBD or colorectal cancer observed in the follow-up period. CONCLUSIONS: In this IBD cohort, surveillance colonoscopy rather than colectomy was found to be safe and effective in patients with NP-CRD after undergoing endoscopic resection. After complete removal of endoscopically resectable NP-CRD, surveillance colonoscopy should be considered a safe and effective first-line strategy rather than colectomy.

EUS-guided Gastroenterostomy: A Multicenter International Study Comparing Benign and Malignant Diseases.

BACKGROUND: Endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE) is a minimally invasive therapy for patients with gastric outlet obstruction without the risks of surgical bypass and the limited long-term efficacy of enteral self-expanding metal stent placement. However, due to its novelty, there is a lack of significant data comparing long-term outcomes of patients with EUS-GE, based on the underlying disease. In this study, we compare outcomes of EUS-GE on benign versus malignant indications. METHODS: Consecutive patients from 12 international, tertiary care centers who underwent EUS-GE over 3 years were extracted in a retrospective registry. Demographic characteristics, procedure-related information and follow-up data was collected. Primary outcome was the rate of adverse events associated with EUS-GE and the comparison of the rate of adverse events in benign versus malignant diseases. Secondary outcomes included technical and clinical success as well as hospitalization admission. RESULTS: A total of 103 patients were included: 72 malignant and 31 benign. The characteristics of the patients undergoing EUS-GE is shown in Table 1. The mean age of the cohort was 68 years and 58 years for malignant and benign etiology. Gender distribution was 57% and 39% being females in malignant and benign etiology group, respectively. Clinical success, technical success, average procedure time, and hospital length of stay were similar in both groups. Patients with benign underlying etiology had significantly higher number of surgically altered midgut anatomy (P=0.0379). CONCLUSION: EUS-GE is equally efficient regardless of the underlying etiology (malignant vs. benign), and the adverse events both groups were comparable.

Machine Boss: rapid prototyping of bioinformatic automata.

MOTIVATION: Many software libraries for using Hidden Markov Models in bioinformatics focus on inference tasks, such as likelihood calculation, parameter-fitting and alignment. However, construction of the state machines can be a laborious task, automation of which would be time-saving and less error-prone. RESULTS: We present Machine Boss, a software tool implementing not just inference and parameter-fitting algorithms, but also a set of operations for manipulating and combining automata. The aim is to make prototyping of bioinformatics HMMs as quick and easy as the construction of regular expressions, with one-line 'recipes' for many common applications. We report data from several illustrative examples involving protein-to-DNA alignment, DNA data storage and nanopore sequence analysis. AVAILABILITY AND IMPLEMENTATION: Machine Boss is released under the BSD-3 open source license and is available from http://machineboss.org/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

JBrowseR: an R interface to the JBrowse 2 genome browser.

MOTIVATION: Genome browsers are an essential tool in genome analysis. Modern genome browsers enable complex and interactive visualization of a wide variety of genomic data modalities. While such browsers are very powerful, they can be challenging to configure and program for bioinformaticians lacking expertise in web development. RESULTS: We have developed an R package that provides an interface to the JBrowse 2 genome browser. The package can be used to configure and customize the browser entirely with R code. The browser can be deployed from the R console, or embedded in Shiny applications or R Markdown documents. AVAILABILITY AND IMPLEMENTATION: JBrowseR is available for download from CRAN, and the source code is openly available from the Github repository at https://github.com/GMOD/JBrowseR/.

Prediction and management of bleeding during endoscopic necrosectomy for pancreatic walled-off necrosis: results of a large retrospective cohort at a tertiary referral center.

BACKGROUND AND AIMS: Lumen-apposing metal stents (LAMSs) provide an endoscopic method for management of walled-off necrosis (WON) and a gateway for the performance of endoscopic necrosectomy (EN). However, bleeding may occur in up to 20% of EN procedures. Predictive factors for bleeding in this patient population are unknown, and there is no agreed-on algorithm for the management of bleeding. The aim of this study was to evaluate preprocedural risk factors for bleeding in patients undergoing endoscopic drainage or EN for WON. METHODS: A retrospective cohort of patients undergoing EN for WON was reviewed. Demographics, comorbidities, concurrent medications, and etiology of pancreatitis were recorded. Pre-, peri-, and postprocedural clinical variables were compared using the χ2 test and independent t test. RESULTS: Between June 2014 and October 2020, 536 ENs were performed in 151 patients. Intraprocedural bleeding occurred during 28 procedures (5.2%) in 18 patients (11.9%). Endoscopic hemostasis was attempted in 8 patients (10 procedures). Eight patients (10 procedures) in total were treated by interventional radiology (IR). Thrombocytopenia (P = .006) and cirrhosis (P = .049) were associated with intraprocedural bleeding, although thrombocytopenia was present in only 1 patient. Identification of a vessel within the cavity endoscopically was also associated with bleeding (P < .001). On multivariate analysis, identification of a vessel within the cavity endoscopically remained a strong predictor of bleeding (P < .001), whereas cirrhosis was no longer significant. Patients who required IR for hemostasis were transfused with significantly more blood before the procedure than patients who did not (3.4 units vs .67 units, P = .002). CONCLUSIONS: EN for WON was associated with a 5.2% per-procedure risk of bleeding and an 11.9% per-patient bleeding risk. Identification of a vessel within the cavity during endoscopy is predictive of bleeding during EN. Patients who require more transfusions before endoscopy may require earlier intervention by IR.

JBrowse Connect: A server API to connect JBrowse instances and users.

We describe JBrowse Connect, an optional expansion to the JBrowse genome browser, targeted at developers. JBrowse Connect allows live messaging, notifications for new annotation tracks, heavy-duty analyses initiated by the user from within the browser, and other dynamic features. We present example applications of JBrowse Connect that allow users 1) to specify and execute BLAST searches by either running on the same host as the webserver, with a self-contained BLAST module leveraging NCBI Blast+ commands, or via a managed Galaxy instance that can optionally run on a different host, and 2) to run the primer design service Primer3. JBrowse Connect allows users to track job progress and view results in the context of the browser. The software is available under a choice of open source licenses including LGPL and the Artistic License.

Cram-JS: reference-based decompression in node and the browser.

MOTIVATION: The CRAM format addresses rising DNA storage costs for short-read sequencing by aligning reads to a reference genome and encoding the resulting alignment with Huffman, subexponential, Elias gamma, rANS, gzip and other codes. The CRAM codec is complex, and until now, there has been no JavaScript implementation. RESULTS: We have developed a JavaScript library, Cram-JS, that natively reads and decompresses the CRAM format on-the-fly. The library is used in the JBrowse and IGV-JS genome browsers and can readily be used by other JavaScript applications, in the web browser or in Node. AVAILABILITY AND IMPLEMENTATION: Cram-JS is written to the ES-6 standard and is available from the GitHub repository at https://github.com/GMOD/cram-js.

Practice patterns of post-ERCP pancreatitis prophylaxis techniques in the United States: a survey of advanced endoscopists.

BACKGROUND AND AIMS: The American Society for Gastrointestinal Endoscopy recommends prophylactic pancreatic duct stent placement (PPS) and rectal nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce the incidence and severity of post-ERCP pancreatitis (PEP) in high-risk individuals and suggests that rectal indomethacin may decrease the risk and severity of PEP in average-risk individuals. The European Society for Gastrointestinal Endoscopy recommends rectal indomethacin for all patients undergoing ERCP. Previous surveys of European endoscopists revealed low adoption of PPS or rectal NSAIDs to prevent PEP. We sought to capture current practice in the prevention of PEP among endoscopists in the United States involved in advanced endoscopy fellowship programs. METHODS: An anonymous online 16-item survey was e-mailed to 233 advanced endoscopists involved in advanced endoscopy fellowship programs. RESULTS: Of the 233 endoscopists who were invited to participate, 62 responded (26.7%). Most respondents reported working in tertiary referral centers (57; 95.0%) and performing ERCP for greater than 5 years (44; 74.6%). All respondents (60; 100.0%) reported working with fellows. Most PPS users (41; 72.0%) reported use of PPS in high-risk patients only and using PPS for PEP in ≤25% of ERCPs (38; 64.4%). Most respondents reported using rectal NSAIDs for high-risk patients only (34; 59.7%) compared with respondents (23; 40.1%) who reported using rectal NSAIDs for prevention of PEP in average-risk patients undergoing ERCP. Most respondents (49; 83.0%) also reported using rapid intravenous fluids to prevent PEP. CONCLUSIONS: Among endoscopists involved in advanced endoscopy fellowships in the United States, rectal NSAIDs are used more frequently than PPS in the prevention of PEP. Despite mounting evidence supporting the use of rectal NSAIDs to prevent PEP in average-risk patients, less than half of the respondents in this survey reported such practice.

Apollo: Democratizing genome annotation.

Genome annotation is the process of identifying the location and function of a genome's encoded features. Improving the biological accuracy of annotation is a complex and iterative process requiring researchers to review and incorporate multiple sources of information such as transcriptome alignments, predictive models based on sequence profiles, and comparisons to features found in related organisms. Because rapidly decreasing costs are enabling an ever-growing number of scientists to incorporate sequencing as a routine laboratory technique, there is widespread demand for tools that can assist in the deliberative analytical review of genomic information. To this end, we present Apollo, an open source software package that enables researchers to efficiently inspect and refine the precise structure and role of genomic features in a graphical browser-based platform. Some of Apollo's newer user interface features include support for real-time collaboration, allowing distributed users to simultaneously edit the same encoded features while also instantly seeing the updates made by other researchers on the same region in a manner similar to Google Docs. Its technical architecture enables Apollo to be integrated into multiple existing genomic analysis pipelines and heterogeneous laboratory workflow platforms. Finally, we consider the implications that Apollo and related applications may have on how the results of genome research are published and made accessible.

Lumen-apposing stents versus plastic stents in the management of pancreatic pseudocysts: a large, comparative, international, multicenter study.

BACKGROUND: Larger caliber lumen-apposing stents (LAMSs) have been increasingly used in the management of pancreatic fluid collections, specifically when solid debris is present; however, their advantages over smaller caliber plastic stents in the management of pancreatic pseudocysts are unclear. The aim of this study was to investigate the safety and efficacy of LAMS specifically in the management of pancreatic pseudocysts compared with double-pigtail plastic stents (DPPSs). METHODS: We performed a multicenter, international, retrospective study between January 2012 and August 2016. A total of 205 patients with a diagnosis of pancreatic pseudocysts were included, 80 patients received LAMSs and 125 received DPPSs. Measured outcomes included clinical success, technical success, adverse events, stent dysfunction, pancreatic pseudocyst recurrence, and need for surgery. RESULTS: Technical success was similar between the LAMS and the DPPS groups (97.5 % vs. 99.2 %; P = 0.32). Clinical success was higher for LAMSs than for DPPSs (96.3 % vs. 87.2 %; P = 0.03). While the need for surgery was similar between the two groups (1.3 % vs. 4.9 %, respectively; P = 0.17), the use of percutaneous drainage was significantly lower in the LAMS group (1.3 % vs. 8.8 %; P = 0.03). At 6-month follow-up, the recurrence rate was similar between the groups (6.7 % vs 18.8 %, respectively; P = 0.12). The rate of adverse events was significantly higher in the DPPS group (7.5 % vs. 17.6 %; P = 0.04). There was no difference in post-procedure mean length of hospital stay (6.3 days [standard deviation 27.9] vs. 3.7 days [5.7]; P = 0.31). CONCLUSION: When compared to DPPSs, LAMSs are a safe, feasible, and effective modality for the treatment of pancreatic pseudocysts and are associated with a higher rate of clinical success, shorter procedure time, less need for percutaneous interventions, and a lower overall rate of adverse events.

Historian: accurate reconstruction of ancestral sequences and evolutionary rates.

Motivation: Reconstruction of ancestral sequence histories, and estimation of parameters like indel rates, are improved by using explicit evolutionary models and summing over uncertain alignments. The previous best tool for this purpose (according to simulation benchmarks) was ProtPal, but this tool was too slow for practical use. Results: Historian combines an efficient reimplementation of the ProtPal algorithm with performance-improving heuristics from other alignment tools. Simulation results on fidelity of rate estimation via ancestral reconstruction, along with evaluations on the structurally informed alignment dataset BAliBase 3.0, recommend Historian over other alignment tools for evolutionary applications. Availability and Implementation: Historian is available at https://github.com/evoldoers/historian under the Creative Commons Attribution 3.0 US license. Contact: ihholmes+historian@gmail.com.

BioMake: a GNU make-compatible utility for declarative workflow management.

MOTIVATION: The Unix 'make' program is widely used in bioinformatics pipelines, but suffers from problems that limit its application to large analysis datasets. These include reliance on file modification times to determine whether a target is stale, lack of support for parallel execution on clusters, and restricted flexibility to extend the underlying logic program. RESULTS: We present BioMake, a make-like utility that is compatible with most features of GNU Make and adds support for popular cluster-based job-queue engines, MD5 signatures as an alternative to timestamps, and logic programming extensions in Prolog. AVAILABILITY AND IMPLEMENTATION: BioMake is available for MacOSX and Linux systems from https://github.com/evoldoers/biomake under the BSD3 license. The only dependency is SWI-Prolog (version 7), available from http://www.swi-prolog.org/. CONTACT: ihholmes + biomake@gmail.com or cmungall + biomake@gmail.com. SUPPLEMENTARY INFORMATION: Feature table comparing BioMake to similar tools. Supplementary data are available at Bioinformatics online.

Solving the master equation for Indels.

BACKGROUND: Despite the long-anticipated possibility of putting sequence alignment on the same footing as statistical phylogenetics, theorists have struggled to develop time-dependent evolutionary models for indels that are as tractable as the analogous models for substitution events. MAIN TEXT: This paper discusses progress in the area of insertion-deletion models, in view of recent work by Ezawa (BMC Bioinformatics 17:304, 2016); (BMC Bioinformatics 17:397, 2016); (BMC Bioinformatics 17:457, 2016) on the calculation of time-dependent gap length distributions in pairwise alignments, and current approaches for extending these approaches from ancestor-descendant pairs to phylogenetic trees. CONCLUSIONS: While approximations that use finite-state machines (Pair HMMs and transducers) currently represent the most practical approach to problems such as sequence alignment and phylogeny, more rigorous approaches that work directly with the matrix exponential of the underlying continuous-time Markov chain also show promise, especially in view of recent advances.

Avulsion is superior to argon plasma coagulation for treatment of visible residual neoplasia during EMR of colorectal polyps (with videos).

BACKGROUND AND AIMS: EMR is used widely for treatment of nonpedunculated colorectal adenomas ≥ 2 cm. Recurrence at the resection site occurs in 10% to 30% of cases. METHODS: Records of consecutive patients referred for endoscopic resection over a 4-year period were reviewed retrospectively. In the first part of the study period, our routine practice was to use argon plasma coagulation (APC) to treat all visible residual neoplasia after exhaustive attempts at snare resection during EMR. In the second part of the study period, we changed our practice to use avulsion to treat all visible residual neoplasia after exhaustive attempts at snare resection during EMR. We analyzed the effect of this change in practice on recurrence rates after EMR. RESULTS: Two hundred twenty-three resected lesions were analyzed. Fifty-nine (26%) were treated with en-bloc EMR, 55 (25%) by piecemeal EMR with complete snare removal of all visible neoplasia, 63 (28%) by piecemeal EMR with APC of visible residual neoplasia, and 46 (21%) by piecemeal EMR with avulsion of visible residual neoplasia. There was no significant difference in adverse event rates among the 4 groups. The recurrence rates on follow-up colonoscopy were 4.2%, 3.0%, 59.3%, and 10.3%, respectively. The recurrence rate for patients treated with avulsion was significantly lower than for those treated with APC (odds ratio, .079; P < .001). Multivariate analysis demonstrated that use of avulsion instead of APC was a significant predictor of no recurrence. CONCLUSIONS: After exhaustive attempts at snare resection during EMR, avulsion is superior to APC for treatment of residual visible neoplasia. Compared with APC, avulsion significantly decreases the recurrence rate without significantly increasing the risk of the procedure.

Combining endoscopic submucosal dissection and endoscopic mucosal resection to treat neoplasia in Barrett's esophagus.

BACKGROUND AND AIMS: Piecemeal endoscopic mucosal resection (EMR) is the standard treatment of nodular Barrett's esophagus dysplasia and T1a cancer. Piecemeal resection may be incomplete and makes precise histologic assessment difficult. Endoscopic submucosal dissection (ESD) is a technique that enables en-bloc resection but has not gained widespread acceptance due to its technical difficulty, risk and long procedure time. METHODS: We developed a protocol consisting of a combination of a limited ESD with supplementary EMR in the same session if necessary, designed to increase en-bloc resection of the most worrisome neoplastic area while maximizing the rate of complete resection of dysplasia. Records of consecutive patients referred for treatment during a 2-year period were reviewed. RESULTS: Eleven patients were treated: two with ESD and nine with combined ESD/EMR. Eight patients had mucosal lesions; three patients had submucosally invasive cancer and were referred to surgery. Five of the 8 mucosal lesions were removed en-bloc by ESD with dysplasia-free margins. Two patients with T1a cancer had low-grade dysplasia in the ESD margins and removal of all dysplasia on EMR. One patient with T1a cancer had high-grade dysplasia in the ESD margins and on EMR. He required a second endoscopy to remove residual neoplasia. There were no adverse events. The mean procedure time was 66.4 ± 15.1 min. CONCLUSIONS: Combining a limited ESD with EMR in the same session enables efficient treatment of visible dysplastic lesions in Barrett's esophagus.

Visualizing next-generation sequencing data with JBrowse.

JBrowse is a web-based genome browser, allowing many sources of data to be visualized, interpreted and navigated in a coherent visual framework. JBrowse uses efficient data structures, pre-generation of image tiles and client-side rendering to provide a fast, interactive browsing experience. Many of JBrowse's design features make it well suited for visualizing high-volume data, such as aligned next-generation sequencing reads.