Advancements in mass spectrometry‐based proteomics have enabled experiments encompassing hundreds of samples. While these large sample sets deliver much‐needed statistical power, handling them introduces technical variability known as batch effects. Here, we present a step‐by‐step protocol for the assessment, normalization, and batch correction of proteomic data. We review established methodologies from related fields and describe solutions specific to proteomic challenges, such as ion intensity drift and missing values in quantitative feature matrices. Finally, we compile a set of techniques that enable control of batch effect adjustment quality. We provide an R package, "proBatch", containing functions required for each step of the protocol. We demonstrate the utility of this methodology on five proteomic datasets each encompassing hundreds of samples and consisting of multiple experimental designs. In conclusion, we provide guidelines and tools to make the extraction of true biological signal from large proteomic studies more robust and transparent, ultimately facilitating reliable and reproducible research in clinical proteomics and systems biology.

Background: Adverse drug events (ADEs) result in excess hospitalizations. Thorough admission medication histories (AMHs) may prevent ADEs; however, the resources required oftentimes outweigh what is available in large hospital settings. Previous risk prediction models embedded into the Electronic Medical Record (EMR) have been used at hospitals to aid in targeting delivery of scarce resources. Objective: To determine if an AMH scoring tool used to allocate resources can decrease 30-day hospital readmissions. Design, Setting, and Participants: Propensity-matched cohort study, Medicine/Surgery patients in large academic safety-net hospital. Intervention or Exposure: Pharmacy-conducted AMHs identified by risk model versus standard of care AMH. Main Outcomes and Measures: A total of 30-day hospital readmissions and inpatient ADE prevention. Results: The model screened 87 240 hospitalizations between June 2017 and June 2019 and 4027 patients per group were included. There were significantly less 30 day readmissions among high-risk identified patients that received a pharmacy-conducted AMH compared to controls (11% vs 15%; P = 0.004) and no significant difference in readmission rates for low-risk patients. While there was significantly higher documentation of major ADE prevention in the pharmacy-led AMH group versus control (1656 vs 12; P < 0.001), there was no difference in electronically-detected inpatient ADEs between groups. Conclusions: A risk tool embedded into the EMR can be used to identify patients whom pharmacy teams can easily target for AMHs. This study showed significant reductions in readmissions for patients identified as high-risk. However, the same benefit in readmissions was not seen in those identified at low-risk, which supports allocating resources to those that will benefit the most.

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BackgroundS-sulphenylation is a ubiquitous protein post-translational modification (PTM) where an S-hydroxyl (−SOH) bond is formed via the reversible oxidation on the Sulfhydryl group of cysteine (C). Recent experimental studies have revealed that S-sulphenylation plays critical roles in many biological functions, such as protein regulation and cell signaling. State-of-the-art bioinformatic advances have facilitated high-throughput in silico screening of protein S-sulphenylation sites, thereby significantly reducing the time and labour costs traditionally required for the experimental investigation of S-sulphenylation.ResultsIn this study, we have proposed a novel hybrid computational framework, termed SIMLIN, for accurate prediction of protein S-sulphenylation sites using a multi-stage neural-network based ensemble-learning model integrating both protein sequence derived and protein structural features. Benchmarking experiments against the current state-of-the-art predictors for S-sulphenylation demonstrated that SIMLIN delivered competitive prediction performance. The empirical studies on the independent testing dataset demonstrated that SIMLIN achieved 88.0% prediction accuracy and an AUC score of 0.82, which outperforms currently existing methods.ConclusionsIn summary, SIMLIN predicts human S-sulphenylation sites with high accuracy thereby facilitating biological hypothesis generation and experimental validation. The web server, datasets, and online instructions are freely available at http://simlin.erc.monash.edu/ for academic purposes.

Background Determining a suitable dose of intravenous colistimethate is challenging because of complicated pharmacokinetics, confusing terminology, and the potential for renal toxicity. Only recently have reliable pharmacokinetic/pharmacodynamic data and dosing recommendations for intravenous colistimethate become available. Objective The aim of this work was to develop a clinician-friendly, easy-to-use mobile app incorporating up-to-date dosing recommendations for intravenous colistimethate in critically ill adult patients. Methods Swift programming language and common libraries were used for the development of an app, ColistinDose, on the iPhone operating system (iOS; Apple Inc). The compatibility among different iOS versions and mobile devices was validated. Dosing calculations were based on equations developed in our recent population pharmacokinetic study. Recommended doses generated by the app were validated by comparison against doses calculated manually using the appropriate equations. Results ColistinDose provides 3 major functionalities, namely (1) calculation of a loading dose, (2) calculation of a daily dose based on the renal function of the patient (including differing types of renal replacement therapies), and (3) retrieval of historical calculation results. It is freely available at the Apple App Store for iOS (version 9 and above). Calculated doses accurately reflected doses recommended in patients with varying degrees of renal function based on the published equations. ColistinDose performs calculations on a local mobile device (iPhone or iPad) without the need for an internet connection. Conclusions With its user-friendly interface, ColistinDose provides an accurate and easy-to-use tool for clinicians to calculate dosage regimens of intravenous colistimethate in critically ill patients with varying degrees of renal function. It has significant potential to avoid the prescribing errors and patient safety issues that currently confound the clinical use of colistimethate, thereby optimizing patient treatment.