Announcing Sorcerer PE v4.0 with Enhanced ETD and Quantitation

Our R&D team is busy working on the next major version of the Sorcerer-PE software, and expects to release it to then-in-warranty customers in the next few weeks.  Early previews and beta tests of some of the components will be made available by arrangement to qualified customer sites.

Highlights of the upcoming release include:

• ETD fragmentation support and analysis
• MUSE scripting modules for rescoring peptide matches with Olsen-Mann and Sadygov-Coon scores
• Interoperation with major components of the Yates lab Sequest suite, including the DTASelect filtering and statistical analysis tool, and the Census quantitation application
• Enhancements to the SEQUEST engine which provide first-pass cross-correlation scoring and E-values for greater accuracy and sensitivity

ETD and phosphorylation form a major focus in our V4.0 release. ETD requires support for new fragmentation patterns, in particular c and z• ions, rather than the b and y ions typical of CID, which currently is what SEQUEST supports. In V4.0, we are introducing c and z• ion support in Sorcerer-Sequest.  Furthermore, to help interpret results, we will offer new scores on the search results to supplement the XCorrs and Evalues from Sequest. The MUSE suite will be extended to include rescoring modules that will offer Olsen-Mann scores and Sadygov-Coon scores (optimized for ETD). Muse results are reported in tab-delimited text tables that are ideal for processing in spreadsheets or database systems.

In this release, we are seeking to build upon SEQUEST’s established strength in sensitive and accurate searching, which owes much to the cross-correlation method and XCorr score it uses. Currently, SEQUEST uses a much coarser ‘Preliminary Score” (Sp) to rapidly filter peptide matches and to identify a much smaller group for which the more accurate XCorr is calculated. However, with optimization of the XCorr calculation, the next generation engines in use on Sorcerer will do the cross-correlation comprehensively in the first pass for all candidate matches. The other traditional SEQUEST scores, including Sp, dCn, etc. will still be computed in the same way so that each peptide match will continue to have the same results — the difference will be that you will now see a match reported that has a strong XCorr final score, even if it has a weak Sp.

Moreover, the new SEQUEST supports the reporting of E-values — a measure of how many matches at least as good as the reported one you can expect to see at random.  This is a measure of the significance of the result that is related to a p-value, and helps to provide a probabilistic interpretation of an XCorr score. (However, note also that it is not at all the same as the probability of the ID being correct or incorrect, which is what PeptideProphet and Scaffold report.)

The SEQUEST marque also encompasses several other very useful applications from the Yates laboratory that extend the value downstream beyond peptide identification. One well-established but recently updated tool that is very popular is DTASelect, which filters and presents the results from SEQUEST, and in the most recent versions authored by Daniel Corciova, also provides statistical analysis including false discovery rate estimation. We have already released a beta of an integration framework of this for Sorcerer V3.5, and we will bundle that up for final release in V4.0.  We continue to improve the integration in collaboration with the Yates lab.

DTASelect support in turn enables use of the Census tool for quantitative analysis, for which the output from DTASelect is required. Census, authored by Robin Park at Scripps, will provide a complete Sorcerer-Muse workflow for SILAC and label-free quantitation in connection with our V4.0 release.

Sorcerer PE V4.0 includes many other enhancements that will improve the power, flexibility and utility of Sorcerer to our customers.  TPP support is updated to version 4.3, which includes a new version of ReAdW, and enhancements to PeptideProphet and ProteinProphet. Scaffold support is improved, too, with a new mechanism for choosing a custom batch template file. A rereleased Muse framework increases the power of this environment and provides new opportunities for customization.

We think you will appreciate the new capabilities and extra value that 4.0 brings. If you are an in-warranty customer, and you would like to check out one or other of the new features as they come on stream for beta testing, then please let us know of your interest!