MaxQuant fails at MSMS_first_search with “Could not find file …\combined\andromeda\aplfiles…” (CreateFile/Open)

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Md Jalal Uddin

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Mar 3, 2026, 1:08:20 PM (7 days ago) Mar 3
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Hi all,
I’m running MaxQuant v2.7.5.0 on a shared Windows workstation and the run consistently fails at MSMS_first_search for all RAW files. The error text (from combined\proc\MSMS_first_search*.error.txt) includes:
Could not find file …\combined\andromeda\aplfiles\…” and references Windows CreateFile/Open (file I/O).

Context:

  • Thermo .raw files (DDA), 6 files total

  • Label-free LFQ, simple search (Trypsin/P; fixed Carbamidomethyl (C); variable Oxidation (M) + Acetyl (Protein N-term))

  • Database is small (Helicobacter pylori G27 proteome FASTA only + contaminants)

  • Failure occurs early (MSMS_first_search), before any results are produced

  • I have tried shortening the output path; issue persists on the shared machine

  • Suspect permissions/storage/path length/AV interference preventing creation of combined\andromeda\aplfiles

Questions:

  1. What typically causes missing/failed creation of andromeda\aplfiles during MSMS_first_search?

  2. Are there recommended settings for output/temp paths on shared/permission-limited PCs (e.g., local temp folder, run as admin)?

  3. Any known issues in v2.7.5.0 related to aplfiles generation or path length, and best workaround?

Thanks very much for any advice.

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