NCBI HomoloGene Database

HomoloGene is an automated system for the detection of homologs among the annotated genes of several completely sequenced eukaryotic genomes. HomoloGene takes protein sequences from differing species and compares them to one another (using blastp) and matches are placed into groups, using a tree built from sequence similarity to guide the process, where closer related organisms are matched up first, and then further organisms are added as the tree is traversed toward the root. The protein alignments are mapped back to their corresponding DNA sequences, where distance metrics can be calculated (e.g. molecular distance, Ka/Ks ratio). Sequences are matched using synteny when applicable. Remaining sequences are matched up by using an algorithm for maximizing the score globally, rather than locally, in a bipartite matching. Cutoffs on bits per position and Ks values are set to prevent unlikely "orthologs" from being grouped together. These cutoffs are calculated based on the respective score distribution for the given groups of organisms. Paralogs are identified by finding sequences that are closer within species than other species.

HomoloGene是一套用于在多个已完成全基因组测序的真核生物基因组注释基因中检测同源基因的自动化系统。该系统从不同物种获取蛋白质序列，使用BLASTp（Basic Local Alignment Search Tool for Proteins）进行两两比对，并依据序列相似度构建的系统发育树指导分组流程：先完成亲缘关系更近的物种间的基因匹配，随后在遍历该树至根节点的过程中逐步纳入亲缘关系更远的物种，最终将匹配结果归入对应组别。将蛋白质比对结果映射回对应的DNA序列后，可计算各类距离指标（例如分子距离、Ka/Ks比值）。若条件允许，会通过同线性（synteny）完成序列匹配。对于剩余未匹配的序列，则采用二分图匹配中的全局最优得分最大化算法进行配对，而非采用局部匹配策略。此外，会设置每位置比特值与Ks值的阈值，以避免可能性极低的"直系同源基因（orthologs）"被错误归为一组，此类阈值将基于对应物种组的得分分布计算得出。旁系同源基因（paralogs）则通过识别物种内序列间的亲缘关系相较于跨物种更为紧密的序列来确定。

搜集汇总

背景与挑战

背景概述

NCBI HomoloGene Database是一个自动化系统，用于检测已完全测序真核生物基因组中注释基因的同源物。它通过比较不同物种的蛋白质序列，结合BLASTP、系统发育树和同线性匹配等方法进行分组，并计算分子距离等指标，同时设置阈值以优化同源物识别和旁系同源物检测。