Dmitry Avtonomov

Postdoctoral Research Fellow

Nesvizhskii Lab

University of Michigan

Biography

I am a Postdoc at Alexey Neshvizhskii’s Lab at the University of Michgan. The main area of research is anything related to mass spectrometry data processing, especially liquid chromatography (LC) and ion mobility (IM) mass spectrometry (LC-MS, IM-MS). I develop mostly in Java, with occasional pieces in C#, Python and C++, some of the projects include:

BatMass - Mass spectrometry data visualization and processing.
MSFragger - Ultra-fast proteomics search engine for Closed and Open searches.
MSFTBX - Java library for MS data files access (mzML, mzXML, pepXML, protXML, mzId, mzIdentML, etc).
IMTBX+Grppr - A suite of tools for extracting signals from Ion Mobility (IM) data (IM-MS, LC-IM-MS) and performing isotopic envelopes detection.
DIA-Umpire - Data Independent Acquisition (DIA) data processing tool that doesn’t require a spectral library.

I started my scientific career at Prof. Eugene Nikolaev’s Ion Physics lab in Moscow. The lab hosted a slew of mass spectrometers, including Thermo LTQ-FT Ultra, Bruker Microflex, Bruker Apex QE, an in-house built 4.7T ICR and multiple ion traps. I supposedly burned the internal wiring for one of the ion traps (Finnigan LCQ Deca XP) during an experiment (there’s no proof it was my fault), but I restored it back to working condition. During this period my focus was on:

Setting up the lab for routine proteomics operations:
- in-house designed and manufactured Nano-ESI ion source
- manufacturing of spraying columns for HPLC (ESI spraying tip integrated with the chromatographic column)
- setting up database search resources (Mascot server at the time)
Negative ion source development for ETD (Electron Transfer Dissociation)
- in-house designed and installed into Finningan LCQ Deca XP
Supercomputer modeling of ion cloud movement in electric and magnetic field
- for simulation of ion cloud motion in ICR mass spectrometers
Development of algorithms for peptide retention time alignment across multiple runs

Interests

Mass Spectrometry
Algorithms
Data Visualization
Ion Mobility
Desktop Applications

Education

PhD, Physics and Mathematics, 2012

Institute for Energy Problems of Chemical Physics
MSc, Applied Physics and Mathematics, 2008

Moscow Institute of Physics and Technology (MIPT)
BSc, Applied Physics and Mathematics, 2006

Moscow Institute of Physics and Technology (MIPT)

Selected Publications

IMTBX and Grppr: Software for Top-Down Proteomics Utilizing Ion Mobility-Mass Spectrometry

Top-down proteomics has emerged as a transformative method for the analysis of protein sequence and post-translational modifications (PTMs). Top-down experiments have historically been performed primarily on ultra-high resolution mass spectrometers due to the complexity of spectra resulting from fragmentation of intact proteins, but recent advances in coupling ion mobility separations to faster, lower resolution mass analyzers now offer a viable alternative. However, software capable of interpreting the highly complex 2-dimensional spectra that result from coupling ion mobility separation to top-down experiments is currently lacking. In this manuscript we present a software suite consisting of 2 programs, IMTBX (IM Toolbox) and Grppr (Grouper), which enable fully automated processing of such data. We demonstrate the capabilities of this software suite by examining a series of intact proteins on a Waters Synapt G2 ion-mobility equipped mass spectrometer, and compare the results to the manual and semi-automated data analysis procedures we have used previously.

Dmitry M. Avtonomov, Daniel A. Polasky, Brandon T. Ruotolo, Alexey I. Nesvizhskii

In Analytical Chemistry, 2017

Preprint Code Project

MSFragger: ultrafast and comprehensive peptide identification in mass spectrometry–based proteomics

We present a fragment-ion indexing method, and its implementation in peptide identification tool MSFragger, that enables a more than 100-fold improvement in speed over most existing proteome database search tools. Using several large proteomic data sets, we demonstrate how MSFragger empowers the open database search concept for comprehensive identification of peptides and all their modified forms, uncovering dramatic differences in modification rates across experimental samples and conditions.

Andy T. Kong, Felipe V. Leprevost, Dmitry M. Avtonomov, Dattatreya Mellacheruvu, Alexey I. Nesvizhskii

In Nature Methods, 2017

Preprint Project

BatMass: a Java Software Platform for LC–MS Data Visualization in Proteomics and Metabolomics

The human brain interprets visual data much better than plain text, hence the saying “a picture is worth a thousand words”. Here, we present the BatMass software package, which allows for performing quick quality control of raw LC–MS data through its fast visualization capabilities. It also serves as a testbed for developers of LC–MS data processing algorithms by providing a data access library for open mass spectrometry file formats and a means of visually mapping processing results back to the original data. We illustrate the utility of BatMass with several use cases of quality control and data exploration.

Dmitry M. Avtonomov, Alexander Raskind, Alexey I. Nesvizhskii

In Journal of Proteome Research, 2016

Preprint Code Project Video

DIA-Umpire: comprehensive computational framework for data-independent acquisition proteomics

DIA-Umpire (http://diaumpire.sourceforge.net/), a comprehensive computational workflow and open-source software for DIA data, detects precursor and fragment chromatographic features and assembles them into pseudo–tandem MS spectra. These spectra can be identified with conventional database-searching and protein-inference tools, allowing sensitive, untargeted analysis of DIA data without the need for a spectral library. Quantification is done with both precursor- and fragment-ion intensities. We demonstrated the performance of the method with control samples of varying complexity and publicly available glycoproteomics and affinity purification–MS data.

Chih-Chiang Tsou, Dmitry M Avtonomov, Brett Larsen, Monika Tucholska, Hyungwon Choi, Anne-Claude Gingras, Alexey I Nesvizhskii

In Nature Methods, 2015

Preprint Project

Projects

BatMass

A framework for LC-MS data visualization and exploration. View spectra, extracted ion chromatograms and 2D ion maps of LC-MS experiments. Synchronized viewers.

MSFTBX: MS File Toolbox

A fast Java library for mass spectrometry data files access (mzML, mzXML, pepXML, protXML, mzId, mzIdentML, etc). Writers for some formats are also available. Available on Maven Central.

IMTBX+Grppr

A suite of tools for extracting signals from Ion Mobility (IM) data (IM-MS, LC-IM-MS) and performing isotopic envelopes detection.

MSFragger

Ultra-fast proteomics search engine. Regular searches - when the precursor mass is limited to a narrow window of several ppm - are done within a few seconds. An “open-search” (with large precursor mass range tolerance, e.g. +/-500 Da) for a 2 hour LC gradient bottom-up proteomics experiment can be done in a minute or so on a laptop.

DIA-Umpire

Data Independent Acquisition (DIA) data processing tool that doens’t require a spectral library. Detects features in MS1 and MS2, correlates precursors to fragments based on elution profile and compiles pseudo-MS/MS spectra which can be searched with standard proteomic search tools.