差异代谢物通路分析
KEGG(Kyoto Encyclopedia of Genes and Genomes)是一个整合了基因组、化学和系统功能信息的数据库[1],各个数据库中包含了大量的有用信息:基因组信息存储在GENES数据库里,包括完整和部分测序的基因组序列;更高级的功能信息存储在PATHWAY数据库里,包括图解的细胞生化过程如代谢、膜转运、信号传递、细胞周期,还包括同系保守的子通路等信息;KEGG的另一个数据 库是LIGAND,包含关于化学物质、酶分子、酶反应等信息。
KEGG提供的整合代谢途径(pathway)查询十分出色,包括碳水化合物、核苷、氨基酸等的代谢及有机物的生物降解,不仅提供了所有可能的代谢途径,而且对催化各步反应的酶进行了全面的注解,包括氨基酸序列、PDB库的链接等。KEGG是进行生物体内代谢分析、代谢网络研究的强有力工具,它有助于研究者把基因及其表达信息作为一个整体网络进行研究。
MetPA是metaboanalyst(www .metaboanalyst.ca)的一部分,主要基于KEGG代谢通路。MetPA数据库通过代谢通路浓缩和拓扑分析,识别出可能的受生物扰动的代谢通路,进而对代谢物的代谢通路进行分析。采用MetPA数据库可以分析两组差异代谢物的相关代谢通路,采用的数据分析算法是超几何检验,pathway拓扑结构采用的是Relative-betweeness Centrality。
图:代谢通路影响因子图
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Total | Hits | Raw p | -log(p) | Holm adjust | FDR | Impact | compounds | pathway | |
---|---|---|---|---|---|---|---|---|---|
Pyrimidine metabolism | 60 | 5 | 0.044772 | 3.1062 | 1 | 1 | 0.14899 | C00299;C00475;C00106;C00239;C00099 | hsa00240 |
Pantothenate and CoA biosynthesis | 27 | 3 | 0.056537 | 2.8729 | 1 | 1 | 0.07286 | C00097;C00099;C00106 | hsa00770 |
Phenylalanine, tyrosine and tryptophan biosynthesis | 27 | 3 | 0.056537 | 2.8729 | 1 | 1 | 0.09964 | C00463;C00079;C02637 | hsa00400 |
beta-Alanine metabolism | 28 | 3 | 0.061871 | 2.7827 | 1 | 1 | 0.28022 | C00099;C00555;C00106 | hsa00410 |
Glycine, serine and threonine metabolism | 48 | 4 | 0.070287 | 2.6552 | 1 | 1 | 0.21997 | C00065;C01026;C00213;C00097 | hsa00260 |
Tyrosine metabolism | 76 | 5 | 0.10142 | 2.2884 | 1 | 1 | 0.1467 | C00788;C03758;C00483;C00232;C05582 | hsa00350 |
Arginine and proline metabolism | 77 | 5 | 0.1058 | 2.2462 | 1 | 1 | 0.07265 | C03564;C00791;C00134;C00555;C00213 | hsa00330 |
Sulfur metabolism | 18 | 2 | 0.11602 | 2.154 | 1 | 1 | 0.03307 | C00065;C00097 | hsa00920 |
Glycerophospholipid metabolism | 39 | 3 | 0.13411 | 2.0091 | 1 | 1 | 0.12685 | C00588;C00346;C00670 | hsa00564 |
Butanoate metabolism | 40 | 3 | 0.14173 | 1.9538 | 1 | 1 | 0.03823 | C01089;C00232;C00741 | hsa00650 |
Galactose metabolism | 41 | 3 | 0.1495 | 1.9005 | 1 | 1 | 0.25441 | C00492;C00124;C00095 | hsa00052 |
Retinol metabolism | 22 | 2 | 0.16131 | 1.8244 | 1 | 1 | 0.09322 | C00473;C11061 | hsa00830 |
Synthesis and degradation of ketone bodies | 6 | 1 | 0.18163 | 1.7058 | 1 | 1 | 0 | C01089 | hsa00072 |
Phenylalanine metabolism | 45 | 3 | 0.18184 | 1.7047 | 1 | 1 | 0.18618 | C00079;C00601;C07086 | hsa00360 |
Sphingolipid metabolism | 25 | 2 | 0.19706 | 1.6242 | 1 | 1 | 0.01288 | C00065;C00346 | hsa00600 |
Cysteine and methionine metabolism | 56 | 3 | 0.27817 | 1.2795 | 1 | 1 | 0.13893 | C00065;C00097;C05527 | hsa00270 |
Pentose phosphate pathway | 32 | 2 | 0.28304 | 1.2622 | 1 | 1 | 0.23357 | C00117;C00345 | hsa00030 |
Methane metabolism | 34 | 2 | 0.30769 | 1.1787 | 1 | 1 | 0.01751 | C01046;C00065 | hsa00680 |
Biotin metabolism | 11 | 1 | 0.30779 | 1.1783 | 1 | 1 | 0.20325 | C00120 | hsa00780 |
Glutathione metabolism | 38 | 2 | 0.35644 | 1.0316 | 1 | 1 | 0.01714 | C00097;C00134 | hsa00480 |
Linoleic acid metabolism | 15 | 1 | 0.39472 | 0.92958 | 1 | 1 | 0 | C06426 | hsa00591 |
Cyanoamino acid metabolism | 16 | 1 | 0.41471 | 0.88018 | 1 | 1 | 0 | C00065 | hsa00460 |
Aminoacyl-tRNA biosynthesis | 75 | 3 | 0.45006 | 0.79838 | 1 | 1 | 0.05634 | C00079;C00097;C00065 | hsa00970 |
Taurine and hypotaurine metabolism | 20 | 1 | 0.48836 | 0.71671 | 1 | 1 | 0 | C00097 | hsa00430 |
Starch and sucrose metabolism | 50 | 2 | 0.4937 | 0.70584 | 1 | 1 | 0 | C00191;C00095 | hsa00500 |
Caffeine metabolism | 21 | 1 | 0.50529 | 0.68262 | 1 | 1 | 0.0305 | C00385 | hsa00232 |
Selenoamino acid metabolism | 22 | 1 | 0.52167 | 0.65072 | 1 | 1 | 0.0241 | C05689 | hsa00450 |
Ether lipid metabolism | 23 | 1 | 0.53751 | 0.6208 | 1 | 1 | 0 | C00670 | hsa00565 |
Thiamine metabolism | 24 | 1 | 0.55284 | 0.59269 | 1 | 1 | 0 | C00097 | hsa00730 |
Alanine, aspartate and glutamate metabolism | 24 | 1 | 0.55284 | 0.59269 | 1 | 1 | 0.05698 | C00232 | hsa00250 |
Valine, leucine and isoleucine biosynthesis | 27 | 1 | 0.59587 | 0.51773 | 1 | 1 | 0.02544 | C00233 | hsa00290 |
alpha-Linolenic acid metabolism | 29 | 1 | 0.62226 | 0.4744 | 1 | 1 | 0 | C16317 | hsa00592 |
Steroid hormone biosynthesis | 99 | 3 | 0.63987 | 0.44649 | 1 | 1 | 0.10682 | C00735;C01176;C05471 | hsa00140 |
Vitamin B6 metabolism | 32 | 1 | 0.65868 | 0.41751 | 1 | 1 | 0 | C00232 | hsa00750 |
Propanoate metabolism | 35 | 1 | 0.69164 | 0.36869 | 1 | 1 | 0.085 | C00099 | hsa00640 |
Ubiquinone and other terpenoid-quinone biosynthesis | 36 | 1 | 0.70191 | 0.35395 | 1 | 1 | 0.01665 | C17010 | hsa00130 |
Inositol phosphate metabolism | 39 | 1 | 0.73073 | 0.31371 | 1 | 1 | 0 | C00191 | hsa00562 |
Nitrogen metabolism | 39 | 1 | 0.73073 | 0.31371 | 1 | 1 | 0 | C00079 | hsa00910 |
Valine, leucine and isoleucine degradation | 40 | 1 | 0.73972 | 0.30149 | 1 | 1 | 0.0421 | C00233 | hsa00280 |
Tryptophan metabolism | 79 | 2 | 0.74146 | 0.29913 | 1 | 1 | 0.05734 | C00463;C00328 | hsa00380 |
Ascorbate and aldarate metabolism | 45 | 1 | 0.78038 | 0.24797 | 1 | 1 | 0.03322 | C00191 | hsa00053 |
Amino sugar and nucleotide sugar metabolism | 88 | 2 | 0.79413 | 0.23051 | 1 | 1 | 0 | C00191;C00124 | hsa00520 |
Lysine degradation | 47 | 1 | 0.79483 | 0.22963 | 1 | 1 | 5.00E-04 | C00408 | hsa00310 |
Fructose and mannose metabolism | 48 | 1 | 0.8017 | 0.22103 | 1 | 1 | 0.04372 | C00095 | hsa00051 |
Fatty acid biosynthesis | 49 | 1 | 0.80834 | 0.21278 | 1 | 1 | 0 | C00712 | hsa00061 |
Purine metabolism | 92 | 2 | 0.81439 | 0.20532 | 1 | 1 | 0.04446 | C00385;C00117 | hsa00230 |
Fatty acid metabolism | 50 | 1 | 0.81476 | 0.20486 | 1 | 1 | 0 | C02990 | hsa00071 |
Pentose and glucuronate interconversions | 53 | 1 | 0.83278 | 0.18299 | 1 | 1 | 0.08723 | C00191 | hsa00040 |
Limonene and pinene degradation | 59 | 1 | 0.86378 | 0.14644 | 1 | 1 | 0.0563 | C07276 | hsa00903 |
Porphyrin and chlorophyll metabolism | 104 | 1 | 0.97123 | 0.029192 | 1 | 1 | 0.01844 | C00500 | hsa00860 |
注:Total,目标代谢通路中代谢物的总数;Hits,目标代谢通路中差异代谢物数量,Raw p,超几何分布检验的p值;-log(p):对p值的自然对数取负值;Holm adjust,Holm假阳性矫正后p值;FDR,假阳性校正后值;Impact,代谢通路影响值;compounds,代谢物KEGG ID;pathway,代谢物代谢通路ID