Extended Data Table 1:

Feature comparison of custom database generation algorithms

Algorithm / Feature	moPepGen	customProDB 16-18	MaxQuant module19	ProteoDisco20	ProteomeGen erator231,32	pypgatk21	pyQUILTS22	samplespecifi cDBGenerator 23-25	sapFinder / PGA26,27	spliceDB28,29	Spritz30
DNA Single Nucleotide Variants	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓
Short DNA Sequence Variants	✓	✓		✓	✓	✓	✓		✓	✓	✓
Short RNA Sequence Variants	✓										✓
Alternative Splice Junctions	✓			✓	✓		✓	✓	✓	✓
Fusion Transcripts	✓			✓	✓		✓	✓	✓	✓
Circular RNAs	✓
Supported Variant Combinations	Any combinations	None	All SNVs only	All SNVs only	All variants only	None	Single SNV with splicing or fusion	None	None	All variants only	None
Modular Support for New Input Formats	✓							✓
Noncoding Transcript Three-Frame Translation	✓				✓	✓			✓
Noncoding Transcript and Short Sequence Variants	✓				✓
Alternative Translation W->P	✓
Export Only Non-canonical Proteotypic Peptides	✓			✓				✓	✓
Summary of Database Generation	✓	✓			✓				✓
Visualization of Database Generation	✓								✓
Database Splitting for Tiered False Discovery Rate Control	✓
Filter FASTA by RNA Abundance	✓				✓			✓