Comet MS/MS

Comet is an open source tandem mass spectrometry (MS/MS) sequence database search tool written primarily in C/C++. The original Comet repository lived on SourceForge since 2012. It was migrated to GitHub on September 2021.

The project website can be found here. This includes release notes and search parameters documentation.

To compile on linux and macOS:

• Type 'make'. This will generate a binary "comet.exe".

To compile with Microsoft Visual Studio:

• We current use build tools v143 with Microsoft Visual Studio 2022.

• Load "Comet.sln" in Visual Studio.

• Set the build to "Release" and "x64".

• Right-mouse-click on the "Comet" project and choose "Build". This should generate a binary "Comet.exe" in x64/Release.

Comet integrates:

• Mike Hoopmann's MSToolkit library for reading various file formats.
• Matthew Belmonte's C implementation of the Twiddle algorithm used in generating modification permutations.
• C++ port of Gygi Lab's AScorePro for modification localization.
• Barak Shoshany's BS::thread_pool C++ thread pool library.
• Thermo Fischer's RawFileReader .Net assembly.

Reading Thermo .raw files on Windows

As of Comet release v2026.02 rev. 1, comet.win64.exe reads Thermo .raw files directly using Thermo's RawFileReader .NET library. This requires two DLLs to be present in the same directory as Comet.exe:

• ThermoFisher.CommonCore.Data.dll
• ThermoFisher.CommonCore.RawFileReader.dll

No installation or registration step is needed -- just place the two files next to Comet.exe (or in the same folder you run Comet from). This is a deliberate improvement over the older MSFileReader COM library Comet used previously, which required a separate installer that registered COM components in the Windows registry.

These DLLs can be obtained from Thermo's official thermofisherlsms/RawFileReader GitHub repo (the Libs/Net471 folder matches the .NET Framework version Comet is built against). Comet has been built and tested against version 5.0.0.93. These two DLLs are also available as release assets in this repository.

CometWrapper.dll and CometWrapperCore.dll (Windows)

Two C++/CLI wrapper assemblies are published as release assets for applications that call Comet's real-time search API from .NET code (for example, RealtimeSearch):

• CometWrapper.dll -- built for .NET Framework 4.7.2.
• CometWrapperCore.dll -- the same wrapper built for .NET 8 (CLRSupport=NetCore). It has a hard dependency on Ijwhost.dll, the .NET shim that loads mixed-mode C++/CLI code, so Ijwhost.dll (also a release asset) must sit in the same directory as CometWrapperCore.dll or the assembly will fail to load.

Both wrappers also need the two Thermo RawFileReader DLLs listed above next to them for .raw input. Neither is needed to run comet.win64.exe itself.

.raw support is Windows-only. mzXML, mzML, and mgf/ms1/ms2-family inputs work on every platform without any of the above and require no additional files.

RawFileReader reading tool. Copyright © 2016 by Thermo Fisher Scientific, Inc. All rights reserved.