1. SORCERER Platform Overview

2. Sorcerer product line Sorcerer 2 well-established standard –Self-contained tower (or 2U rack unit) –Can fit under bench, shared by lab –One high-end processing node, with integrated storage –Good match for single Orbi or similar Sorcerer Enterprise new HT platform –Pre-integrated rack cabinet –Goes in server room, shared site-wide –Includes multinode blade server with high capacity storage subsystem –Ideal for multi-instrument throughput

3. Sorcerers Primergy hardware platform Sorcerer 2 on Primergy platform – Came out in 2008 – Introducing 3 rd rev in Q3 this year – Further uptick in CPU and system components SNR-Fujitsu partnership developed with Sorcerer 2 – Joint platform design – Testing and tuning – Manufacturing – Worldwide field support Enables Enterprise platform – Collaboration for optimal blade server, storage and interconnect design – Result: takes throughput to next level with high performance and scalability

4. Sorcerer 2 server evolution System ModelSilver box (rev2)Primergy TX300S4Primergy TX300 S5Primergy TX300 S6 # CPUs2222 Cores/CPUDualQuad # Sorcerer jobs6888 CPU architecturePaxvilleHarpertownNehalemWestmere Rel CPU integer throughput.* 44% (est.) 100%204%215% * SPECint*_rate_base2006 20092010200820112007

5. Sorcerer Enterprise platform Goal: scalable analysis throughput for multiple instruments – More data to analyze, more data to keep – Faster scan rates, e.g. Orbi Velos – Multi-vendor instrumentation – Broad array of applications and downstream analysis – Needs most sensitive searching Solution: Sorcerer Enterprise on blade server – Primergy BX900 server with up to 18 blades Each blade has more processing power than a Sorcerer 2 – Eternus DX80 ~9TB disk space in base configuration, expandable up to ~180TB (Sorcerer 2: ~2TB available disk space) RAID-6 for extra data integrity and redundancy

6. Sorcerer Enterprise under the hood Components in base config – Primergy BX9oo blade server: 10U (17½) chassis with 18 slots 1 build-in high speed interconnect blade 2× (up to 18×) BX920 blades, each with: 8 Nehalem cores, 36GB RAM, 2×76GB fast SAS drives, built-in ethernet – Eternus DX80 disk storage system Each module can hold 12 disks (450GB SAS or 1TB nearline) iSCSI fast connection – Integrated in rack with UPS, network switch etc. Externally – One Ethernet port, one IP address (plug-and-play)

7. Sequest 3G What is it? – Next generation Sequest – keeps (and extends) its gold standard sensitivity – evolves for modern proteomics Key benefits of the technology – optimized for high-throughput searching of large data sets – digital signal processing techniques improve sensitivity for noisy spectra – provides robust PTM search – support for new fragmentation techniques such as ETD – extensions to SEQUEST 3G enable multiple similarity scores for improved specificity

8. Sequest 3G on Sorcerer Key Steps: 1.Fast but accurate spectrum matching that uses ppm mass accuracy 2.Complete "on the fly" consideration of chosen PTMs 3.All candidate matches (not just a "short list") get rigorous cross-correlation scores... 4.... to enable most sensitive ranking and effective compilation of results 5.Comprehensive XCorrs also allow reliable E-value results for simple interpretation, as well as computation of legacy SEQUEST scores

9. Sorcerer PE Software V4.0 beta Sorcerer Enterprise distributed searching TPP v4.3.1 Support for Scaffold V3.0 Sequest 3G initial release Muse: new scripts – Integration with DTASelect, Census, APEX, etc. – New Versasearch combined ETD/CID analysis New license manager facilitates better performance with more system resources – Better Sorcerer Enterprise performance Coming Msconvert support will handle Xcalibur 2.1 Raw files Bug fixes and minor updates

10. Muse Example: DTASelect and Census Great tools for filtering, reporting and quant from Yates Lab – Available from Yates lab (fields.scripps.edu) – We recommend it for SILAC etc. (commercial offering in development) On Sorcerer, install scripts and run census_select.muse – Runs DTASelect, then Census – View DTASelect report directly from Sorcerer Web GUI – Runs Census pre-analysis using search results and supplied params/config census_select.muse -c ~/custom/census/census_config_silac.xml

11. VersaSearch for combined CID/ETD Unified search accommodates ETD variations All-CID, all-ETD, alternating, & decision tree Peptide terminus mods to account for b vs c, y vs. z-radical Post-processing to define true vs. decoy Post-search re-scoring provides other similarity scores E.g. binomial scores User-defined fragmentation models SEQUEST 3G Peptide ID Extract peaklist Protein Inference RAW peaks pep hits prot hits Determine CID vs. ETD Tag True/Decoy w/ MUSE Peptide FDR w/ terminus mods