MOLECULAR SEQUENCE DATA

前所未有的DNA和蛋白质序列的积累(包括 完整的大肠杆菌物理图谱和第一个完整的核苷酸 真核细胞染色体序列(酵母第三号染色体) 在组织和分析方面的挑战和机遇。我们的 拟议的研究将集中在数学、统计、计算、 以及这种背景下的信息学问题。主要议题为(一) 基于分数的序列分析的统计理论及应用 (Ii)非均质性Rho-Scan统计的理论和应用 序列内和序列间的评估；(3)计算机的发展 蛋白质和核苷酸序列的统计分析程序 (SAPS和SANS)；(Iv)寡核苷酸组成偏向的研究 包括稀有和频繁寡核苷酸的特征；(V) DNA间距离度量和排序的定义及应用 序列。基于分数的序列分析方法被广泛使用，两者 关于单个序列(例如，水动力图)和 关于序列比较(例如BLAST)。相关概率 对于得分较高的总和，将推导出分布近似 段，匹配的最大对齐分数 是随机向量(例如，表示同时充电， 氨基酸的疏水性和空间属性)。电脑 将设计算法来计算以下情况的近似概率 给定的参数集。Rho扫描评估分布中的异常 沿着一条线的标记(例如，限制位点、特殊的 寡核苷酸、核小体定位)。这一理论将会得到发展 为了适应与指定理论分布的偏差，以及 用于多个序列之间的数据比较。这些计划将 除上述方法外，还实施了大量其他统计 (例如，具有多变量分位数的成分评估 分布；紧密重复和紧密二联体的计数和间距)和 应该对实验的设计有所帮助。评估方法 基于的寡核苷酸组成偏差和距离度量 建议使用寡核苷酸组成来评估差异和 序列之间和序列内的相似性，尤其与 功能/结构作用和系统发育重建。集约化 将对大的基因组序列进行详细的研究 比较目的和确定特殊区域(起源于 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).