UCHIME2 is an algorithm for detecting chimeric sequences . It is an update of the UCHIME algorithm with some new features. It is implemented in the uchime2_ref command. See UCHIME2 paper for details.
The uchmie2_denovo command is obsolete. It is replaced by the uchime3_denovo command which implements the chimera filtering step in unoise3 . This the same algorithm described in the UCHIME2 paper, except that parameters have been adjusted to reduce the number of false positives.
     
      I do not recommend using uchime2_ref in a 16S or ITS analysis pipeline
     
     . The problem is that you will get high rates of both FPs and FNs unless you have denoised sequences, in which case the chimera removal is a special case which is built into the denoising code
     
      (see
      
       UCHIME2 paper
      
      for details).
     
     
     
     It is better to use
     
      unoise3
     
     or
     
      cluster_otus
     
     for chimera filtering. I believe that unoise is a better approach because it has better resolution: it reconstructs the biological sequences in the reads without 97% clustering. This enables you to resolve species and strains which are >97% similar to each other.
    
     I recommend you use the
     
      largest available reference database
     
     for uchime2_ref, e.g. SILVA for 16S or UNITE for ITS. My previous advice to use a small, high-quality database was misguided (
     
      
       wrong!
      
     
     )-- you need a large database to get decent sensitivity, a small database like "gold" will probably be missing many parents in practice.