AUTHOR=Fang Gang , Liang Hanjie TITLE=An Integrated Algorithm for Designing Oligodeoxynucleotides for Gene Synthesis JOURNAL=Frontiers in Genetics VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.836108 DOI=10.3389/fgene.2022.836108 ISSN=1664-8021 ABSTRACT=Design and construction of large synthetic genes can be a slow, difficult and confusing process, especially in the key step of oligodeoxynucleotides design. Herein we present an integrated algorithm to design oligonucleotide sets for gene synthesis by both ligase chain reaction (LCR) and polymerase chain reaction (PCR). It offers much flexibility with no constraints on gene to be synthesized. Firstly, it divides the long input DNA sequence by a greedy algorithm based on the length of oligodeoxynucleotides overlap region. Secondly, it tunes the length of overlap region iteratively in attempt to minimize the melting temperatures variance of overlap. Thirdly, dynamic programming algorithm is used to achieve uniform melting temperatures of oligodeoxynucleotide overlaps. Finally, the oligodeoxynucleotides with homologous melting temperature necessary for LCR-based or two-step assembly PCR-based synthesis of the desired gene are outputted.