About HS-SEQ

HS-SEQ is the first de novo sequencing algorithm designed specifically for identifying heparan sulfate (HS) isomer using high resolution tandem mass spectrometry. It is able to provide product-grade identification performance within seconds or minutes.

Principle

HS-SEQ deals with ambiguous HS tandem MS data. Due to the repeating disaccharide units of HS and lability of sulfate groups, peaks in the tandem MS spectra are easily to assigned to multiple fragment structures, leading to ambiguous evidence for sulfation localization. HS-SEQ constructs a graph based on the most confident peak interpretations, and expands the graph by integrating the currently most confident peak interpretations (Bayesian inference). The graph can be converted into a modification localization profile -- "modification distribution", which allows the prediction of sulfation/acetylation sites. The computation time only depends on the number of peak interpretations, and is independent of the total candidate space.

Performance Demonstration

| Test data | Modification distribution (dp15 for demo) | |:--------------|:----------------------------------------------| | | |

Downloads

Program(v1.0.2): https://glycan-pipeline.googlecode.com/svn/trunk/GAG/bin/hsseq_v1.0.2.zip

Usage

Step 0: Deisotoping/deconvolution (generating monoisotopic peak list, for Solarix only, to be uploaded)

simplefinder.exe -s spectrum_file -p 245.000 -z 4- -o output_file -e 1

Step 1: Peak interpretation (Optional)

librarymatch.exe -c composition_file -m monoisotopic_peak_list -o output_file -e 2

• type "librarymatch.exe -h" for help.
  
• composition_file example can be found from directory "structure"
  
• monoisotopic_peak_list example can be found from directory "data" in the format: m/z intensity z

step 2: Sequencing

hsseq -c composition_file -m monoisotopic_peak_list -o output_file -e 2

• type "hsseq.exe -h" for help.
  

Example

hsseq.exe -c structure\arixtra.gl -m data\arixtra_4_NETD_mo
no_list.txt

https://glycan-pipeline.googlecode.com/svn/trunk/GAG/image/hs-seq-output.JPG'>https://glycan-pipeline.googlecode.com/svn/trunk/GAG/image/hs-seq-output.JPG

Contact

The program was developed by Han Hu(hh1985@bu.edu)
PI: Prof. Joseph Zaia (jzaia@bu.edu) and Prof. Yu (Brandon) Xia (brandon.xia@mcgill.ca)

Reference

Hu, H. et al. A Computational Framework for Heparan Sulfate Sequencing Using High-resolution Tandem Mass Spectra. Mol Cell Proteomics mcp.M114.039560 (2014). doi:10.1074/mcp.M114.039560 http://www.mcponline.org/content/early/2014/06/12/mcp.M114.039560.abstract'>[Link]