Search bioRxiv⌕ Search

Biology subjects

Kirkwood-Donelson, K. I.

Publications and source records attributed to Kirkwood-Donelson, K. I..

3 recordsLinked to original sources

The Everything Bagel Feature Finder: Ultra-fast automated feature finding for untargeted metabolomics

Metabolomics studies are increasingly being applied with hundreds to thousands, even tens of thousands of samples that demand rapid, automated data processing while maintaining analytical sensitivity or quantitative accuracy. A major computational bottleneck is feature finding, which is the transformation of LC-MS and LC-MS/MS data into a set of analyte signals aligned and quantified across samples. Feature finding can be computationally intensive and often requires manual iterative parameter optimization. To accelerate this process, we present the Everything Bagel (EB) feature finder, an ultra-fast automated feature finding tool that integrates feature detection, retention-time alignment, and gap filling designed for run-time and memory efficiency. We benchmarked EB against two automated feature finding methods on eight benchmarking datasets. Specifically, we evaluated these three feature finding methods by measuring spike-in standard detection coverage, dilution series quantification accuracy, and yeast 12C/13C credentialed features. In this evaluation, the EB feature finder achieved performance comparable to, and often exceeding, existing methods while requiring up to 150-fold lower CPU hours and up to 113-fold lower wall time. We further demonstrated the bioanalytical validity of EB by reanalyzing published datasets used for biomarker discovery and reproduced biologically significant features that matched the published findings using manually tuned feature finding settings. Taken along with the speed improvements, we anticipate EB will enhance the ability to automatically analyze datasets with thousands to tens of thousands of samples for the community.

bioinformatics↗

Updated Guidance for Communicating PFAS Identification Confidence with Ion Mobility Spectrometry

Over the last decade, global contamination from per- and polyfluoroalkyl substances (PFAS) has become apparent due to their detection in countless matrices worldwide, from consumer products to human blood to drinking water. As researchers implement non-targeted analyses (NTA) to more fully understand the PFAS present in the environment and human bodies, clear guidance is needed for consistent and objective reporting of the identified molecules. Confidence levels for small molecules analyzed and identified with high-resolution mass spectrometry (HRMS) have existed since 2014; however, unification of currently-used levels and improved guidance for their application is needed due to inconsistencies in reporting and continuing innovations in analytical methods. Here, we (i) investigate current practices for confidence level reporting of PFAS identified with liquid chromatography (LC), gas chromatography (GC), and/or ion mobility spectrometry (IMS) coupled with HRMS and (ii) propose a simple, unified confidence level guidance that incorporates both PFAS-specific attributes and IMS collision cross section (CCS) values. SynopsisUnified and simplified requirements to guide confidence level assignment in non-targeted PFAS identification efforts with ion mobility spectrometry. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/634925v2_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1b9808dorg.highwire.dtl.DTLVardef@1a6e663org.highwire.dtl.DTLVardef@5f8813org.highwire.dtl.DTLVardef@1dea0d1_HPS_FORMAT_FIGEXP M_FIG For Table of Contents only C_FIG

scientific communication and education↗

Proteomic and Lipidomic Plasma Evaluations Reveal Biomarkers for Domoic Acid Toxicosis in California Sea Lions

Domoic acid is a neurotoxin secreted by the marine diatom genus, Pseudo-nitzschia, during toxic algal bloom events. California sea lions (Zalophus californianus) are exposed to domoic acid through ingestion of fish that feed on toxic diatoms, resulting in a domoic acid toxicosis (DAT), which can vary from mild to fatal. Sea lions with mild disease can be treated if toxicosis is detected early after exposure, therefore, rapid diagnosis of DAT is essential but also challenging. In this work, we performed multi-omics analyses, specifically proteomic and lipidomic, on blood samples from 31 California sea lions. Fourteen sea lions were diagnosed with DAT based on clinical signs and postmortem histological examination of brain tissue, and 17 had no evidence of DAT. Proteomic analyses revealed three apolipoproteins with statistically significant lower abundance in the DAT individuals compared to the non-DAT individuals. These proteins are known to transport lipids in the blood. Lipidomic analyses highlighted 29 lipid levels that were statistically different in the DAT versus non-DAT comparison, 28 of which were downregulated while only one was upregulated. Furthermore, of the 28 downregulated lipids, 15 were triglycerides, illustrating their connection with the perturbed apolipoproteins and showing their potential for use in rapid DAT diagnoses. SYNOPSISMulti-omics evaluations reveal blood apolipoproteins and triglycerides are altered in domoic acid toxicosis in California sea lions. GRAPHIC ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/592757v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@b61289org.highwire.dtl.DTLVardef@17ae9f7org.highwire.dtl.DTLVardef@96904eorg.highwire.dtl.DTLVardef@dc299a_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗