antisense dna parameters derived from next-nearest-neighbor analysis of experimental data反义dna参数来源于next-nearest-neighbor实验数据的分析.pdfVIP

Gray et al. BMC Bioinformatics 2010, 11:252 /1471-2105/11/252 R E S E A R C H A R T I C L E Open Access Research article Antisense DNA parameters derived from next-nearest-neighbor analysis of experimental data 1 1 1,2 1 Donald M Gray* , Carla W Gray , Byong-Hoon Yoo and Tzu-Fang Lou Abstract Background: The enumeration of tetrameric and ot her sequence motifs that are positively or negatively correlated with in vivo antisense DNA effects has been a useful addition to the arsenal of information needed to predict effective targets for antisense DNA control of gene expression. Such retrospective information derived from in vivo cellular experiments characterizes aspects of the sequence dependence of antisense inhibition that are not predicted by nearest-neighbor (NN) thermodynamic parameters derived from in vitro experiments. However, quantitation of the antisense contributions of motifs is problematic, since individual motifs are not isolated from the effects of neighboring nucleotides, and motifs may be overlapping. These problems are circumvented by a next-nearest-neighbor (NNN) analysis of antisense DNA effects in which the overlapping nature of nearest-neighbors is taken into account. Results: Next-nearest-neighbor triplet combinations of nucleotides are the simplest that include overlapping sequence effects and therefore can encompass interactions beyond those of nearest neighbors. We used singular value decomposition (SVD) to fit experimental data from our laboratory in which phosphorothioate-modified antisense DNAs (S-DNAs) 20 nucleotides long were used to inhibit cellular protein expression in 112 experiments involving four gene targets and two cell lines. Data were fitted using a NNN model, neglecting end effects, to d