Chimera: The spoiler in multiple displacement amplification

Multiple displacement amplification (MDA) based on isothermal random priming and high fidelity phi29 DNA polymerase-mediated processive extension has revolutionized the field of whole genome amplification by enabling the amplification of minute amounts of DNA, such as from a single cell, generating vast amounts of DNA with high genome coverage. Despite its advantages, MDA has its own challenges, one of the grandest being the formation of chimeric sequences (chimeras), which presents in all MDA products and seriously disturbs the downstream analysis. In this review, we provide a comprehensive overview of current research on MDA chimeras. We first reviewed the mechanisms of chimera formation and chimera detection methods. We then systematically summarized the characteristics of chimeras, including overlap, chimeric distance, chimeric density, and chimeric rate, as found in independently published sequencing data. Finally, we reviewed the methods used to process chimeric sequences and their impacts on the improvement of data utilization efficiency. The information presented in this review will be useful for those interested in understanding the challenges with MDA and in improving its performance.