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Quick start for USEARCH v5 users
Most of the code in USEARCH was re-written between versions 5 and 6. The following table summarizes the most important improvements and changes.
Change   Comments
Command line   The command line has been redesigned. It is not backwards compatible with v5. I understand the importance of backwards compatibility and regret the inconvenience this will cause for some users. This was necessary because the underlying code has changed so much that simulating the old command line was simply not possible. In v6, the command line is easier to understand. Options are consistently supported across most commands, and error messages are issued for invalid combinations of options.
Faster and smaller   Some commands are significantly faster and/or smaller than their equivalents in v5. Smaller means less memory. These improvements are data-dependent, so your performance may vary. In rare cases, performance may be slightly worse.
Multithreading   Most search and clustering commands, including chimera-finding, now support multithreading. This can give significant  speed improvements on multi-core CPUs. For example, on my 12-core i7 desktop PC, UCHIME is about 10x faster in reference database mode.
Identity definition   In version 6, USEARCH always uses the BLAST definition of identity.
Increased number of clusters   The changed identity definition tends to increase the number of clusters at a given identity compared with v5, but this does not indicate reduced sensitivity. See cluster quality and sequence identity.
Database files   Most search commands now support both FASTA and the UDB database file format. This format combines features of the old .udb and .wdb formats. Note that UDB files built with v6 are not compatible with v5, and vice versa. In v6, UDB files are compatible between 32- and 64-bit binaries. The database file is specified with the ‑db option; the format (FASTA or UDB) is detected automatically.
Obsoleted commands   Some commands are no longer supported, including uhire and ustar. The -msaout option replaces ustar.