Molecular Isotopic Distribution Analysis (MIDAs) with Adjustable Mass Accuracy

Abstract

In this paper, we present Molecular Isotopic Distribution Analysis (MIDAs), a new software tool designed to compute molecular isotopic distributions with adjustable accuracies. MIDAs offers two algorithms, one polynomial-based and one Fourier-transform-based, both of which compute molecular isotopic distributions accurately and efficiently. The polynomial-based algorithm contains few novel aspects, whereas the Fourier-transform-based algorithm consists mainly of improvements to other existing Fourier-transform-based algorithms. We have benchmarked the performance of the two algorithms implemented in MIDAs with that of eight software packages (BRAIN, Emass, Mercury, Mercury5, NeutronCluster, Qmass, JFC, IC) using a consensus set of benchmark molecules. Under the proposed evaluation criteria, MIDAs’s algorithms, JFC, and Emass compute with comparable accuracy the coarse-grained (low-resolution) isotopic distributions and are more accurate than the other software packages. For fine-grained isotopic distributions, we compared IC, MIDAs’s polynomial algorithm, and MIDAs’s Fourier transform algorithm. Among the three, IC and MIDAs’s polynomial algorithm compute isotopic distributions that better resemble their corresponding exact fine-grained (high-resolution) isotopic distributions. MIDAs can be accessed freely through a user-friendly web-interface at http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/midas/index.html.Graphical abstractᅟ

A Simple Light Isotope Metabolic Labeling (SLIM-labeling) Strategy: A Powerful Tool to Address the Dynamics of Proteome Variations In Vivo

“…A key step in the analytic process is to extract 12 C abundance from the isotope clusters for each peptide. Here we show that the experimental isotope clusters fit remarkably well with the theoretical clusters computed using the MIDAS webserver at the NCBI (http://www.ncbi.nlm.nih.gov/CBBresearch/qmbp/ midas/index.html) (17), making it possible to generate high quality calibration standards for 12 C enrichment measurements. We believe that this strategy for in vivo protein labeling may contribute significantly to the development of new approaches to explore key features of proteome dynamics.…”

MQ: Tool for HR-AM Based Quantitative Analysis for Direct MS Workflow

“…In order to accomplish this, a rigorous set of constraints that take into account high mass accuracies for peak qualification along with naturally present isotopic peak distributions are widely accepted criteria [8,14,11]. MQ incorporates the efficient MIDAs algorithm [1] for relative isotopic abundance confirmation towards this end. A high-throughput database query workflow and PCA based multivariate clustering analysis can further benefit qualitative elucidations.…”

“…Various reports in past decade highlighted significance of RAID over and above mass accuracy offered by ultra-high resolution MS in characterization of analytes assertively [8,14]. In case of complex and large molecules, prediction of RAID becomes more complicated and computationally intensive [1,12]. In a recent publication, a web based tool for Molecular Isotopic Distribution Analysis (MIDAs) was developed with two improved algorithms for RAID calculation based on polynomial and Fourier-transform methods, having better performance in comparison to published tools for RAID estimation [1].…”

“…In case of complex and large molecules, prediction of RAID becomes more complicated and computationally intensive [1,12]. In a recent publication, a web based tool for Molecular Isotopic Distribution Analysis (MIDAs) was developed with two improved algorithms for RAID calculation based on polynomial and Fourier-transform methods, having better performance in comparison to published tools for RAID estimation [1]. In MQ, an implementation of polynomial based algorithm from MIDAs web tool for fine grained RAID (used with high-resolution MS) estimation has been incorporated.…”

“…These constraints are function of natural abundance of isotopes and elemental composition of analyte. Further details of algorithm can be found in article by Alves G. et al [1].…”