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 | |
---|---|---|---|---|---|---|---|---|---|
Aminoacyl-tRNA biosynthesis | 52 | 7 | 0.00022065 | 8.4189 | 0.059135 | 0.012004 | 0.13393 | C00025;C00037;C00065;C00079;C00148;C00188;C00407 | mmu00970 |
Glyoxylate and dicarboxylate metabolism | 62 | 6 | 0.003645 | 5.6144 | 0.97322 | 0.16524 | 0.20513 | C00025;C00037;C00065;C00158;C00209;C00258 | mmu00630 |
Glycine, serine and threonine metabolism | 50 | 5 | 0.0068875 | 4.978 | 1 | 0.26763 | 0.2764 | C00037;C00065;C00188;C00258;C05519 | mmu00260 |
Pentose and glucuronate interconversions | 56 | 5 | 0.011081 | 4.5025 | 1 | 0.37675 | 0.094828 | C00116;C00379;C00476;C01904;C02266 | mmu00040 |
Valine, leucine and isoleucine biosynthesis | 23 | 3 | 0.0175 | 4.0455 | 1 | 0.5289 | 0.16129 | C00188;C00407;C02226 | mmu00290 |
Galactose metabolism | 46 | 4 | 0.024803 | 3.6968 | 1 | 0.64645 | 0.047619 | C00089;C00116;C00794;C01235 | mmu00052 |
Alanine, aspartate and glutamate metabolism | 28 | 3 | 0.029673 | 3.5175 | 1 | 0.64645 | 0.19886 | C00025;C00158;C00232 | mmu00250 |
Ascorbate and aldarate metabolism | 50 | 4 | 0.032538 | 3.4253 | 1 | 0.64645 | 0.14286 | C00818;C00879;C01040;C01620 | mmu00053 |
Synaptic vesicle cycle | 12 | 2 | 0.033209 | 3.4049 | 1 | 0.64645 | 0.16667 | C00025;C00037 | mmu04721 |
Biosynthesis of unsaturated fatty acids | 74 | 5 | 0.033273 | 3.403 | 1 | 0.64645 | 0.09375 | C00249;C01530;C01595;C06427;C08281 | mmu01040 |
Taste transduction | 32 | 3 | 0.041917 | 3.1721 | 1 | 0.7601 | 0.078947 | C00025;C00089;C00158 | mmu04742 |
Sphingolipid signaling pathway | 15 | 2 | 0.050403 | 2.9877 | 1 | 0.83275 | 0.2069 | C00065;C00319 | mmu04071 |
Pentose phosphate pathway | 35 | 3 | 0.052522 | 2.9465 | 1 | 0.83275 | 0.13433 | C00121;C00258;C05345 | mmu00030 |
Phenylalanine metabolism | 60 | 4 | 0.057454 | 2.8568 | 1 | 0.83275 | 0.095238 | C00079;C00423;C00805;C05853 | mmu00360 |
Proximal tubule bicarbonate reclamation | 17 | 2 | 0.063275 | 2.7603 | 1 | 0.83275 | 0.10619 | C00025;C00074 | mmu04964 |
Glutathione metabolism | 38 | 3 | 0.064293 | 2.7443 | 1 | 0.83275 | 0.11888 | C00025;C00037;C00134 | mmu00480 |
Glycerolipid metabolism | 38 | 3 | 0.064293 | 2.7443 | 1 | 0.83275 | 0.26623 | C00093;C00116;C00258 | mmu00561 |
Retrograde endocannabinoid signaling | 19 | 2 | 0.077122 | 2.5624 | 1 | 0.9535 | 0.10526 | C00025;C00116 | mmu04723 |
Citrate cycle (TCA cycle) | 20 | 2 | 0.084372 | 2.4725 | 1 | 0.99779 | 0.033333 | C00074;C00158 | mmu00020 |
Apoptosis | 4 | 1 | 0.094254 | 2.3618 | 1 | 1 | 0.25 | C00319 | mmu04210 |
Arginine biosynthesis | 23 | 2 | 0.10726 | 2.2325 | 1 | 1 | 0.10692 | C00025;C00624 | mmu00220 |
FoxO signaling pathway | 5 | 1 | 0.11641 | 2.1506 | 1 | 1 | 0.2 | C00025 | mmu04068 |
Sphingolipid metabolism | 25 | 2 | 0.12333 | 2.0929 | 1 | 1 | 0.10959 | C00065;C00319 | mmu00600 |
Glucagon signaling pathway | 26 | 2 | 0.13158 | 2.0281 | 1 | 1 | 0.090909 | C00074;C00158 | mmu04922 |
Huntington disease | 6 | 1 | 0.13804 | 1.9802 | 1 | 1 | 0.16667 | C00025 | mmu05016 |
Fructose and mannose metabolism | 54 | 3 | 0.14404 | 1.9376 | 1 | 1 | 0.16667 | C00636;C00794;C05345 | mmu00051 |
Cocaine addiction | 7 | 1 | 0.15913 | 1.838 | 1 | 1 | 0.090909 | C00025 | mmu05030 |
Spinocerebellar ataxia | 7 | 1 | 0.15913 | 1.838 | 1 | 1 | 0.14286 | C00025 | mmu05017 |
Nicotine addiction | 7 | 1 | 0.15913 | 1.838 | 1 | 1 | 0.14286 | C00025 | mmu05033 |
Long-term potentiation | 7 | 1 | 0.15913 | 1.838 | 1 | 1 | 0.14286 | C00025 | mmu04720 |
Fatty acid biosynthesis | 58 | 3 | 0.16757 | 1.7864 | 1 | 1 | 0.021947 | C00249;C01530;C06424 | mmu00061 |
Glycolysis / Gluconeogenesis | 31 | 2 | 0.17446 | 1.7461 | 1 | 1 | 0.12448 | C00074;C05345 | mmu00010 |
Glutamatergic synapse | 8 | 1 | 0.17972 | 1.7163 | 1 | 1 | 0.2 | C00025 | mmu04724 |
Amphetamine addiction | 9 | 1 | 0.19982 | 1.6104 | 1 | 1 | 0.076923 | C00025 | mmu05031 |
Circadian entrainment | 9 | 1 | 0.19982 | 1.6104 | 1 | 1 | 0.11111 | C00025 | mmu04713 |
Long-term depression | 9 | 1 | 0.19982 | 1.6104 | 1 | 1 | 0.11111 | C00025 | mmu04730 |
GABAergic synapse | 9 | 1 | 0.19982 | 1.6104 | 1 | 1 | 0.23529 | C00025 | mmu04727 |
Phenylalanine, tyrosine and tryptophan biosynthesis | 34 | 2 | 0.20115 | 1.6037 | 1 | 1 | 0.078947 | C00074;C00079 | mmu00400 |
Pyrimidine metabolism | 65 | 3 | 0.21113 | 1.5553 | 1 | 1 | 0.1002 | C00178;C00295;C00299 | mmu00240 |
Alcoholism | 10 | 1 | 0.21942 | 1.5168 | 1 | 1 | 0.071429 | C00025 | mmu05034 |
Necroptosis | 10 | 1 | 0.21942 | 1.5168 | 1 | 1 | 0.083333 | C00319 | mmu04217 |
Pertussis | 10 | 1 | 0.21942 | 1.5168 | 1 | 1 | 0.1 | C00253 | mmu05133 |
Phospholipase D signaling pathway | 11 | 1 | 0.23855 | 1.4332 | 1 | 1 | 0.047619 | C00025 | mmu04072 |
D-Arginine and D-ornithine metabolism | 11 | 1 | 0.23855 | 1.4332 | 1 | 1 | 0.066667 | C00134 | mmu00472 |
Gap junction | 11 | 1 | 0.23855 | 1.4332 | 1 | 1 | 0.090909 | C00025 | mmu04540 |
Choline metabolism in cancer | 11 | 1 | 0.23855 | 1.4332 | 1 | 1 | 0.10112 | C00093 | mmu05231 |
Butanoate metabolism | 42 | 2 | 0.274 | 1.2946 | 1 | 1 | 0.088235 | C00025;C00232 | mmu00650 |
D-Glutamine and D-glutamate metabolism | 13 | 1 | 0.27543 | 1.2894 | 1 | 1 | 0.14286 | C00025 | mmu00471 |
Amyotrophic lateral sclerosis | 14 | 1 | 0.29321 | 1.2269 | 1 | 1 | 0.055556 | C00025 | mmu05014 |
Regulation of lipolysis in adipocytes | 14 | 1 | 0.29321 | 1.2269 | 1 | 1 | 0.14286 | C00116 | mmu04923 |
Arginine and proline metabolism | 78 | 3 | 0.29714 | 1.2136 | 1 | 1 | 0.20343 | C00025;C00134;C00148 | mmu00330 |
Lysine degradation | 50 | 2 | 0.34673 | 1.0592 | 1 | 1 | 0.019481 | C00037;C00408 | mmu00310 |
Neuroactive ligand-receptor interaction | 52 | 2 | 0.36461 | 1.0089 | 1 | 1 | 0.038462 | C00025;C00037 | mmu04080 |
Glycerophospholipid metabolism | 52 | 2 | 0.36461 | 1.0089 | 1 | 1 | 0.10185 | C00093;C00623 | mmu00564 |
Nitrogen metabolism | 19 | 1 | 0.37582 | 0.97865 | 1 | 1 | 0.090909 | C00025 | mmu00910 |
Nicotinate and nicotinamide metabolism | 55 | 2 | 0.39108 | 0.93885 | 1 | 1 | 0.12093 | C00232;C00253 | mmu00760 |
Phosphonate and phosphinate metabolism | 56 | 2 | 0.3998 | 0.9168 | 1 | 1 | 0.029412 | C00037;C00074 | mmu00440 |
Caffeine metabolism | 22 | 1 | 0.42073 | 0.86576 | 1 | 1 | 0.029412 | C07481 | mmu00232 |
Taurine and hypotaurine metabolism | 22 | 1 | 0.42073 | 0.86576 | 1 | 1 | 0.029412 | C00025 | mmu00430 |
Thermogenesis | 23 | 1 | 0.43498 | 0.83246 | 1 | 1 | 0.10256 | C00116 | mmu04714 |
Carbohydrate digestion and absorption | 27 | 1 | 0.48859 | 0.71623 | 1 | 1 | 0.034483 | C00089 | mmu04973 |
Linoleic acid metabolism | 28 | 1 | 0.50119 | 0.69077 | 1 | 1 | 0.13158 | C01595 | mmu00591 |
Phosphatidylinositol signaling system | 29 | 1 | 0.51348 | 0.66654 | 1 | 1 | 0.0091603 | C03546 | mmu04070 |
Vitamin B6 metabolism | 29 | 1 | 0.51348 | 0.66654 | 1 | 1 | 0.014925 | C00232 | mmu00750 |
Ferroptosis | 29 | 1 | 0.51348 | 0.66654 | 1 | 1 | 0.069767 | C00025 | mmu04216 |
Pyruvate metabolism | 31 | 1 | 0.53718 | 0.62143 | 1 | 1 | 0.020408 | C00074 | mmu00620 |
Thiamine metabolism | 31 | 1 | 0.53718 | 0.62143 | 1 | 1 | 0.022222 | C00037 | mmu00730 |
Pathways of neurodegeneration - multiple diseases | 32 | 1 | 0.54859 | 0.6004 | 1 | 1 | 0.020833 | C00025 | mmu05022 |
Sulfur metabolism | 33 | 1 | 0.55973 | 0.5803 | 1 | 1 | 0.018182 | C00065 | mmu00920 |
Starch and sucrose metabolism | 37 | 1 | 0.60163 | 0.50811 | 1 | 1 | 0.0082645 | C00089 | mmu00500 |
Fatty acid elongation | 40 | 1 | 0.63044 | 0.46133 | 1 | 1 | 0.0054348 | C00249 | mmu00062 |
Valine, leucine and isoleucine degradation | 42 | 1 | 0.6485 | 0.43309 | 1 | 1 | 0.021739 | C00407 | mmu00280 |
Ubiquinone and other terpenoid-quinone biosynthesis | 92 | 2 | 0.66476 | 0.40833 | 1 | 1 | 0.05 | C00156;C00423 | mmu00130 |
alpha-Linolenic acid metabolism | 44 | 1 | 0.66569 | 0.40694 | 1 | 1 | 0.030303 | C06427 | mmu00592 |
Purine metabolism | 95 | 2 | 0.68207 | 0.38262 | 1 | 1 | 0.0036101 | C00037;C00209 | mmu00230 |
Porphyrin and chlorophyll metabolism | 142 | 3 | 0.6829 | 0.38141 | 1 | 1 | 0.02549 | C00025;C00037;C00188 | mmu00860 |
Inositol phosphate metabolism | 47 | 1 | 0.68992 | 0.37118 | 1 | 1 | 0.0095012 | C03546 | mmu00562 |
Histidine metabolism | 47 | 1 | 0.68992 | 0.37118 | 1 | 1 | 0.032 | C00025 | mmu00340 |
Primary bile acid biosynthesis | 47 | 1 | 0.68992 | 0.37118 | 1 | 1 | 0.04878 | C00037 | mmu00120 |
Fatty acid degradation | 50 | 1 | 0.71242 | 0.33909 | 1 | 1 | 0.0090909 | C00249 | mmu00071 |
Amino sugar and nucleotide sugar metabolism | 108 | 2 | 0.74891 | 0.28913 | 1 | 1 | 0.044828 | C00636;C05345 | mmu00520 |
Folate biosynthesis | 58 | 1 | 0.76483 | 0.26811 | 1 | 1 | 0.0048077 | C00156 | mmu00790 |
Cysteine and methionine metabolism | 63 | 1 | 0.79267 | 0.23235 | 1 | 1 | 0.044386 | C00065 | mmu00270 |
Tyrosine metabolism | 78 | 1 | 0.8581 | 0.15304 | 1 | 1 | 0.004 | C00232 | mmu00350 |
Neomycin, kanamycin and gentamicin biosynthesis | 81 | 1 | 0.86849 | 0.141 | 1 | 1 | 0.012048 | C00025 | mmu00524 |
Bile secretion | 97 | 1 | 0.91244 | 0.09163 | 1 | 1 | 0.0091743 | C00805 | mmu04976 |
ABC transporters | 138 | 16 | 1.1345e-07 | 15.992 | 3.0859e-05 | 3.0859e-05 | 0.11594 | C00025;C00037;C00065;C00079;C00089;C00093;C00116;C00121;C00134;C00148;C00188;C00299;C00379;C00407;C00503;C00794 | mmu02010 |
Protein digestion and absorption | 47 | 8 | 1.3018e-05 | 11.249 | 0.003515 | 0.0011803 | 0.17021 | C00025;C00037;C00065;C00079;C00134;C00148;C00188;C00407 | mmu04974 |
Central carbon metabolism in cancer | 37 | 8 | 1.9487e-06 | 13.148 | 0.0005281 | 0.00026503 | 0.18868 | C00025;C00037;C00065;C00074;C00079;C00148;C00158;C00407 | mmu05230 |
Mineral absorption | 29 | 6 | 5.3551e-05 | 9.8349 | 0.014405 | 0.0036415 | 0.17143 | C00037;C00065;C00079;C00148;C00188;C00407 | mmu04978 |
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