Various sources of error affect the hybrid selection (HS) process. Pre-adapter artifacts are those that arise in the preparation step(s) prior to the ligation of the PCR adapters. These artifacts occur on the original template strand, before the addition of adapters, so they correlate with read number orientation in a specific way.

A classic example is the shearing of target genomic DNA leading to oxidation of an amine of guanine at position 8 8-oxoguanine (8-OxoG, OxoG) (doi:10.1093/nar/gks1443) (see entry on OxoG in this Dictionary for more details).

Bait bias (single bait bias or reference bias artifact) is a type of artifact that affects data generated through hybrid selection methods.

These artifacts occur during or after the target selection step, and correlate with substitution rates that are biased or higher for sites having one base on the reference/positive strand relative to sites having the complementary base on that strand. For example, a G>T artifact during the target selection step might result in a higher (G>T)/(C>A) substitution rate at sites with a G on the positive strand (and C on the negative), relative to sites with the flip (C positive)/(G negative). This is known as the G-Ref artifact.