MOLECULAR SEQUENCE DATA

DNA和蛋白质序列的空前积累（包括 完整的E.大肠杆菌和第一个完整的核苷酸 真核生物染色体（酵母染色体III）的序列构成了 组织和分析方面的挑战和机遇。 我们 拟议的研究将集中在数学，统计，计算， 和信息学问题。 主要议题是（一） 基于分数的序列分析的统计理论与应用; (ii)非均匀性的rho- scan统计理论及应用 序列内部和序列之间的评估;（iii）开发计算机 蛋白质和核苷酸序列的统计分析程序 (SAPS和SANS）;（iv）寡核苷酸组成偏差的研究 包括稀有和常见寡核苷酸的表征;（v） DNA间距离测度和排序的定义及应用 序列的 基于分数的序列分析方法被广泛使用， 对于单个序列（例如，亲水性图）， 在序列比较方面（例如BLAST）。 相关概率 分布近似值将从高得分的总和中得出， 段，在得分为 是随机向量（表示，例如，同时充电， 疏水性和氨基酸的空间属性）。 计算机 将设计算法来计算近似概率， 设置参数。Rho扫描评估分布中的异常 标记沿着一条线（例如限制性位点，特殊的 寡核苷酸、核小体放置）。 这个理论将得到发展 以适应与指定理论分布的偏差， 用于多个序列之间的数据比较。 这些程序将 除了上述方法之外，还实现了大量其他统计 (e.g.,多变量分位数的成分评价 分布;紧密重复和紧密二联体的计数和间距）和 应该有助于实验的设计 评价方法 寡核苷酸组成偏差和距离测量基于 提出了寡核苷酸组合物来评估差异， 序列之间和序列内的相似性，特别与 功能/结构角色和系统发育重建。 密集 将对大型基因组序列进行详细研究， 比较目的，并确定特别区域（ 复制、调控序列和结构元件）。

The unprecedented accumulation of DNA and protein sequence (including the complete physical map of E. coli and the first complete nucleotide sequence of a eukaryotic chromosome (yeast chromosome III) poses challenges and opportunities in terms of organization and analysis. Our proposed research will focus on mathematical, statistical, computational, and informatics problems in this context. Main topics are (i) statistical theory and applications of score-based sequence analysis; (ii) theory and applications of rho- scan statistics for heterogeneity assessments within and among sequences; (iii) development of computer programs for the statistical analysis of protein and nucleotide sequences (SAPS and SANS); (iv) studies on oligonucleotides compositional biases including characterizations of rare and frequent oligonucleotides; (v) definitions and applications of distance measures and orderings among DNA sequences. Score-based sequence analysis methods are in wide use, both with respect to single sequences (e.g., hydropathy plots) and with respect to sequence comparisons (e.g. BLAST). Relevant probability distributions approximations will be derived for sums of high scoring segments, the maximal matching alignment score in the case that scores are random vectors (representing, for example, simultaneously charge, hydrophobicity, and steric attributes of an amino acid). Computer algorithms will be devised to calculate approximate probabilities for given sets of parameters. Rho-scans assess anomalies in the distribution of markers along a line (e.g. restriction sites, special oligonucleotides, nucleosome placements). The theory will be developed to accommodate deviations from a specified theoretical distribution and for data comparisons among several sequences. These programs will implement in addition to above methods a large number of other statistics (e.g., compositional evaluations with multivariate quantile distributions; counts and spacings of close repeats and close dyads) and should help with the design of experiments. Methods for evaluating oligonucleotide compositional biases and distance measures based on oligonucleotide composition are proposed to assess differences and similarities among and within sequences, with particular relevance to functional/structural roles and phylogenetic reconstructions. Intensive detailed studies on large genomic sequences will be conducted for comparative purposes and to identify special regions (origin of replications, regulatory sequences, and structural elements).