Peak PickPeak Pick“A Modern, Computational Approach to Analyzing “A Modern, Computational Approach to Analyzing

Protein Mass Spectra”Protein Mass Spectra”

Nelson YoungNelson YoungLab PresentationLab Presentation

Dec 11,2003Dec 11,2003

M/Z – Proteometrics’ Solution (http://65.219.84.5/moverzDL.html)M/Z – Proteometrics’ Solution (http://65.219.84.5/moverzDL.html)

PeakFinder – Efeckta's Solution (http://www.efeckta.com)PeakFinder – Efeckta's Solution (http://www.efeckta.com)

Peak Pick – MS SolutionPeak Pick – MS Solution

Other SolutionsOther Solutions

PeakFinder – Efeckta's Solution PeakFinder – Efeckta's Solution (http://www.efeckta.com)(http://www.efeckta.com)

Bruker’s Software (Instrumental software)Bruker’s Software (Instrumental software)

Analyst QS – Biomics’ Solution Analyst QS – Biomics’ Solution http://www.biomics.co.kr/products/software/softwhttp://www.biomics.co.kr/products/software/software_08.htmare_08.htm

Peak Pick – AlgorithmPeak Pick – Algorithm

Plot the mass spectrum based on the input text filePlot the mass spectrum based on the input text fileDraw the optimal baseline to filter out the background Draw the optimal baseline to filter out the background noisenoise– Typically, noise decreases gradually as m/z increases Typically, noise decreases gradually as m/z increases – Baseline changes w.r.t. noise and is always 1-2 times greater Baseline changes w.r.t. noise and is always 1-2 times greater

than noise.than noise.– Baseline determined by using the ‘windowing’ methodBaseline determined by using the ‘windowing’ method– Test and trial to find the optimal size for the window Test and trial to find the optimal size for the window

Group the remaining clusters of points to form candidate Group the remaining clusters of points to form candidate peakspeaksMinimum peak width measuring from the base of the Minimum peak width measuring from the base of the peak is 10 mz (usually over 100 pts!)peak is 10 mz (usually over 100 pts!)

Peak Pick – Algorithm (Cont’d)Peak Pick – Algorithm (Cont’d)

Point with the highest intensity determines the peak’s mz Point with the highest intensity determines the peak’s mz valuevalueIf height of peak is 2-3 times greater than the height of If height of peak is 2-3 times greater than the height of baseline-noise, then label it as ‘valid’ peak. Peak-to-baseline-noise, then label it as ‘valid’ peak. Peak-to-noise ratio decreases as m/z increases noise ratio decreases as m/z increases Resolve internal peaks if necessaryResolve internal peaks if necessary– A labeled peak may contain multiple internal peaks if baseline is A labeled peak may contain multiple internal peaks if baseline is

too low!too low!

Find the correlation among peaks (singly-charged, Find the correlation among peaks (singly-charged, doubly-charged, triply-charged)doubly-charged, triply-charged)Peaks below 1000 mz are ignored – mostly instrumental Peaks below 1000 mz are ignored – mostly instrumental noise noise That’s it to the algorithm! Sounds easy, eh? Now, That’s it to the algorithm! Sounds easy, eh? Now, consider these scenarios ….consider these scenarios ….

Peak Pick – ScenariosPeak Pick – Scenarios

1.)What if baseline is too low that peaks are hidden and areconsider as part of a larger peak (internal peaks)?2.)How to determine the base of the peaks?3.)What if peak still fails to be labeled?

Peak Pick – Redefine Peak RegionPeak Pick – Redefine Peak Region

Peak Pick – Redefine Peak RegionPeak Pick – Redefine Peak Region

Peak Pick – Overview (Features)Peak Pick – Overview (Features)

Rubber-band zoom / Undo zoom operationsRubber-band zoom / Undo zoom operationsAutomatic peak labeling in bounded regionAutomatic peak labeling in bounded region– Pick all the peaks if bounded region is whole spectrumPick all the peaks if bounded region is whole spectrum

Manually identify or erase peaksManually identify or erase peaksInteractive display of mz and intensity values on mouse Interactive display of mz and intensity values on mouse movementmovementExport spectrum on display in PNG image formatExport spectrum on display in PNG image formatExport peak list in either text or MS Excel formatExport peak list in either text or MS Excel formatColor labeling for different types of peaks (singly - , Color labeling for different types of peaks (singly - , doubly - , triply – charged ions)doubly - , triply – charged ions)Handle MS and MS/MS mass spectraHandle MS and MS/MS mass spectra

Peak Pick – Overview (Input/Output)Peak Pick – Overview (Input/Output)

Peak Pick – Overview (GUI)Peak Pick – Overview (GUI)

Peak Pick – Overview (Export)Peak Pick – Overview (Export)

Peak Pick -- AdvantagesPeak Pick -- Advantages

Highly portable to many different platformsHighly portable to many different platforms– Windows, Unix/Linux, Macintosh, Solaris, SGIWindows, Unix/Linux, Macintosh, Solaris, SGI

No installation requiredNo installation required– Window’s Drag&DropWindow’s Drag&Drop– Console’s Command Line Console’s Command Line

Fast startupFast startup– No dependency of librariesNo dependency of libraries

Multiple simultaneous workspaces for spectral Multiple simultaneous workspaces for spectral viewing and manipulationviewing and manipulationHandle both types of mass spectra: MS and Handle both types of mass spectra: MS and MS/MSMS/MS

Peak Pick – Advantages (Cont’d)Peak Pick – Advantages (Cont’d)

Simple, intuitive GUISimple, intuitive GUI– No parameters or tolerances to setNo parameters or tolerances to set– No prior knowledge or expertise in analyzing mass No prior knowledge or expertise in analyzing mass

spectraspectra

Effective, efficient peak picking algorithm (>95%)Effective, efficient peak picking algorithm (>95%)– No fixed threshold across the spectrum, No fixed threshold across the spectrum,

Textual and graphical outputsTextual and graphical outputs‘‘Smart’ correlated peak labeling schemaSmart’ correlated peak labeling schemaManual and automatic peak labelingManual and automatic peak labeling

Peak Pick -- DisadvantagesPeak Pick -- Disadvantages

Need Java Runtime Environment (JRE) to Need Java Runtime Environment (JRE) to run programrun program

Show current zoom position w.r.t. to the Show current zoom position w.r.t. to the whole spectrumwhole spectrum

Cannot read or write files to networkCannot read or write files to network

GUI – inconsistent with standard, GUI – inconsistent with standard, commercial productscommercial products

Future WorkFuture Work

Automate iterative zooms between Automate iterative zooms between adjacent peaks to improve peak picking adjacent peaks to improve peak picking algorithmalgorithm

Accept more file formats for input mass Accept more file formats for input mass spectraspectra

Process mass spectra in batch modeProcess mass spectra in batch mode

More image formats for outputMore image formats for output

Future Work (Cont’d)Future Work (Cont’d)

Create transparent images to facilitate overlaid Create transparent images to facilitate overlaid and comparison of spectral images and comparison of spectral images

Allow reading and writing of files to networkAllow reading and writing of files to network

Make it public, preferably a web application Make it public, preferably a web application – Applet front-end, servlet back-endApplet front-end, servlet back-end– Online submission of mass spectra Online submission of mass spectra

Toggle display of peak labels on/offToggle display of peak labels on/off

AcknowledgementsAcknowledgements

Dr. David WishartDr. David Wishart

Dr. Liang LiDr. Liang Li

Dr. Gary Van DomselaarDr. Gary Van Domselaar

Haiyan ZhangHaiyan Zhang

HongzingHongzing

ShiLaiShiLai