Topic 8. 克隆进化之 RobustClone

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已于 2022-02-15 13:39:48 修改

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分类专栏：肿瘤克隆进化生信分析文章标签： r语言开发语言

于 2022-01-06 15:56:30 首次发布

本文链接：https://blog.csdn.net/weixin_41368414/article/details/122345593

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肿瘤克隆进化生信分析专栏收录该内容

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**上一期介绍了 Cardelino 的使用，这期介绍RobustClone，我们知道单细胞数据的SNV和CNV检出率都是非常低的，那么怎么有效的获得可使用的突变位点是重中之重，那么该软件包RobustClone利用PCA模式对单细胞数据进行降维，以此来获得更加准确的突变位点达到对单细胞克隆演化的推断。**

**动机：**单细胞测序数据为肿瘤内的异质性提供了前所未有的见解。利用单细胞测序可以更好地表征克隆基因型，并重建肿瘤细胞/克隆的系统发育关系。然而，单细胞测序数据往往容易出错，使其计算分析具有挑战性。

**结果：**为了从容易出错的单细胞测序数据推断肿瘤中的克隆进化，开发了一个高效的计算框架，称为 RobustClone。该算法基于扩展稳健主成分分析和低秩矩阵分解方法，恢复了亚克隆的真实基因型，并重建了亚克隆进化树。RobustClone 是一种无模型的方法，可以应用于单细胞单核苷酸变异 (scSNV) 和单细胞拷贝数变异 (scCNV) 数据。它是高效的和可扩展的大规模数据集。我们对模拟数据集进行了一套系统的评估，证明在大规模数据中，RobustClone 在准确性和效率方面都优于最先进的方法。我们进一步在两个 scSNV 和两个 scCNV 数据集上验证了RobustClone 的有效性，证明其能够在不同场景下准确地恢复基因型矩阵并推断出亚克隆进化树。特别是，在 10X Genomics scCNV 大规模乳腺癌数据集上，RobustClone 揭示了亚克隆进化的空间进展模式。

关于安装问题

该软件包是用 MATLAB 和 R 语言写的，所以使用之前需要准备安装 MATLAB。

关于输入文件

该软件包输入的数据为SNV或CNV数据。对于SNV数据，可以有两种方式：

如果是二进制数据，包括三种元素即 0，1，3

0 表示非突变位点；
1 表示突变位点；
3 表示缺失位点。

如果是三元数据，包括四种元素即 0，1，2，3

0 表示非突变位点；
1 表示突变杂合位点；
2 表示突变纯合位点；
3 表示缺失位点。

该软件包给出来的例子，如下：

  SNV1  SNV2  SNV3  SNV4  SNV5  SNV6  SNV7  SNV8  SNV9  SNV10  SNV11  SNV12  SNV13  SNV14  SNV15  SNV16  SNV17  SNV18  SNV19  SNV20  SNV21  SNV22  SNV23  SNV24  SNV25  SNV26  SNV27  SNV28  SNV29  SNV30  SNV31  SNV32  SNV33  SNV34  SNV35  SNV36  SNV37  SNV38  SNV39  SNV40  SNV41  SNV42  SNV43  SNV44  SNV45  SNV46  SNV47  SNV48  SNV49  SNV50  SNV51  SNV52  SNV53  SNV54  SNV55  SNV56  SNV57  SNV58  SNV59  SNV60  SNV61  SNV62  SNV63  SNV64  SNV65  SNV66  SNV67  SNV68  SNV69  SNV70  SNV71  SNV72  SNV73  SNV74  SNV75  SNV76  SNV77  SNV78  SNV79  SNV80  SNV81  SNV82  SNV83  SNV84  SNV85  SNV86  SNV87  SNV88  SNV89  SNV90  SNV91  SNV92  SNV93  SNV94  SNV95  SNV96  SNV97  SNV98  SNV99  SNV100  SNV101  SNV102  SNV103  SNV104  SNV105  SNV106  SNV107  SNV108  SNV109  SNV110  SNV111  SNV112  SNV113  SNV114  SNV115  SNV116  SNV117  SNV118  SNV119  SNV120  SNV121  SNV122  SNV123  SNV124  SNV125  SNV126  SNV127  SNV128  SNV129  SNV130  SNV131  SNV132  SNV133  SNV134  SNV135  SNV136  SNV137  SNV138  SNV139  SNV140  SNV141  SNV142  SNV143  SNV144  SNV145  SNV146  SNV147  SNV148  SNV149  SNV150  SNV151  SNV152  SNV153  SNV154  SNV155  SNV156  SNV157  SNV158  SNV159  SNV160  SNV161  SNV162  SNV163  SNV164  SNV165  SNV166  SNV167  SNV168  SNV169  SNV170  SNV171  SNV172  SNV173  SNV174  SNV175  SNV176  SNV177  SNV178  SNV179  SNV180  SNV181  SNV182  SNV183  SNV184  SNV185  SNV186  SNV187  SNV188  SNV189  SNV190  SNV191  SNV192  SNV193  SNV194  SNV195  SNV196  SNV197  SNV198  SNV199  SNV200  SNV201  SNV202  SNV203  SNV204  SNV205  SNV206  SNV207  SNV208  SNV209  SNV210  SNV211  SNV212  SNV213  SNV214  SNV215  SNV216  SNV217  SNV218  SNV219  SNV220  SNV221  SNV222  SNV223  SNV224  SNV225  SNV226  SNV227  SNV228  SNV229  SNV230  SNV231  SNV232  SNV233  SNV234  SNV235  SNV236  SNV237  SNV238  SNV239  SNV240  SNV241  SNV242  SNV243  SNV244  SNV245  SNV246  SNV247  SNV248  SNV249  SNV250  SNV251  SNV252  SNV253  SNV254  SNV255  SNV256  SNV257  SNV258  SNV259  SNV260  SNV261  SNV262  SNV263  SNV264  SNV265  SNV266  SNV267  SNV268  SNV269  SNV270  SNV271  SNV272  SNV273  SNV274  SNV275  SNV276  SNV277  SNV278  SNV279  SNV280  SNV281  SNV282  SNV283  SNV284  SNV285  SNV286  SNV287  SNV288  SNV289  SNV290  SNV291  SNV292  SNV293  SNV294  SNV295  SNV296  SNV297  SNV298  SNV299  SNV300  SNV301  SNV302  SNV303  SNV304  SNV305  SNV306  SNV307  SNV308  SNV309  SNV310  SNV311  SNV312  SNV313  SNV314  SNV315  SNV316  SNV317  SNV318  SNV319  SNV320  SNV321  SNV322  SNV323  SNV324  SNV325  SNV326  SNV327  SNV328  SNV329  SNV330  SNV331  SNV332  SNV333  SNV334  SNV335  SNV336  SNV337  SNV338  SNV339  SNV340  SNV341  SNV342  SNV343  SNV344  SNV345  SNV346  SNV347  SNV348  SNV349  SNV350  SNV351  SNV352  SNV353  SNV354  SNV355  SNV356  SNV357  SNV358  SNV359  SNV360  SNV361  SNV362  SNV363  SNV364  SNV365  SNV366  SNV367  SNV368  SNV369  SNV370  SNV371  SNV372  SNV373  SNV374  SNV375  SNV376  SNV377  SNV378  SNV379  SNV380  SNV381  SNV382  SNV383  SNV384  SNV385  SNV386  SNV387  SNV388  SNV389  SNV390  SNV391  SNV392  SNV393  SNV394  SNV395  SNV396  SNV397  SNV398  SNV399  SNV400  SNV401  SNV402  SNV403  SNV404  SNV405  SNV406  SNV407  SNV408  SNV409  SNV410  SNV411  SNV412  SNV413  SNV414  SNV415  SNV416  SNV417  SNV418  SNV419  SNV420  SNV421  SNV422  SNV423  SNV424  SNV425  SNV426  SNV427  SNV428  SNV429  SNV430  SNV431  SNV432  SNV433  SNV434  SNV435  SNV436  SNV437  SNV438  SNV439  SNV440  SNV441  SNV442  SNV443  SNV444  SNV445  SNV446  SNV447  SNV448  SNV449  SNV450  SNV451  SNV452  SNV453  SNV454  SNV455  SNV456  SNV457  SNV458  SNV459  SNV460  SNV461  SNV462  SNV463  SNV464  SNV465  SNV466  SNV467  SNV468  SNV469  SNV470  SNV471  SNV472  SNV473  SNV474  SNV475  SNV476  SNV477  SNV478  SNV479  SNV480  SNV481  SNV482  SNV483  SNV484  SNV485  SNV486  SNV487  SNV488  SNV489  SNV490  SNV491  SNV492  SNV493  SNV494  SNV495  SNV496  SNV497  SNV498  SNV499  SNV500
cell1  3  3  0  0  0  0  1  0  1  0  0  0  0  0  1  0  0  3  0  0  3  0  0  3  0  0  3  0  0  3  0  0  0  0  1  0  0  0  0  0  1  0  1  0  0  1  1  0  3  0  3  1  0  1  1  3  0  3  1  0  0  0  0  3  0  3  1  0  0  0  3  3  3  0  1  3  3  3  1  3  3  1  3  1  0  0  1  0  1  1  1  0  0  3  0  3  1  3  0  0  0  0  0  1  1  3  1  0  3  0  3  3  3  0  1  0  1  1  1  3  0  0  0  1  0  0  3  0  3  1  0  0  3  1  3  0  0  1  0  0  1  0  0  0  0  3  0  0  1  0  0  0  0  0  0  0  0  0  1  0  3  0  0  0  0  0  0  3  0  0  0  0  1  0  0  1  3  0  3  0  3  1  0  0  0  0  1  0  0  0  1  0  0  1  3  0  0  0  0  0  0  1  3  3  0  0  3  0  0  3  3  0  0  0  0  1  0  3  3  0  3  0  0  0  3  1  0  3  0  0  3  3  0  0  0  1  1  3  1  1  0  3  0  0  3  1  0  0  0  3  1  3  0  1  1  1  0  3  0  3  3  0  1  0  0  0  0  0  3  0  0  1  3  3  0  0  0  0  0  0  3  3  0  1  0  3  0  0  1  0  0  0  0  3  0  0  0  1  1  1  0  0  0  0  0  3  3  0  0  0  0  0  0  3  0  0  0  0  0  3  0  0  0  0  1  1  3  0  1  0  0  0  0  0  1  0  0  1  1  0  0  0  0  1  0  0  0  1  1  0  0  0  0  3  0  1  0  1  0  0  0  0  0  0  3  0  0  0  0  0  0  3  0  3  0  0  0  0  0  0  3  3  0  0  3  0  0  1  0  0  0  0  0  1  0  0  0  0  3  0  0  1  3  0  3  0  0  0  1  3  0  0  0  0  0  0  0  1  0  0  3  0  0  3  0  0  0  0  0  0  0  0  0  0  0  0  0  0  3  1  3  3  0  0  0  1  1  3  3  1  1  0  0  0  0  3  1  0  0  1  0  0  0  3  0  1  0  0  0  0  0  0  0  0  3  0  0  0  0  0  0  0  0  3  1  1  3  0  0  0  3  1  3  3  0  1  0  0  0  0
cell2  0  0  1  0  1  3  3  3  1  0  0  0  1  1  0  1  1  0  0  0  0  3  3  1  0  0  0  3  1  3  1  0  1  1  1  1  3  3  0  0  3  1  1  0  0  1  3  0  3  0  3  0  3  0  0  1  1  0  3  0  0  3  3  1  0  1  3  3  3  0  3  1  3  1  1  0  0  3  1  1  0  1  1  1  1  0  1  1  0  1  3  1  1  0  0  0  1  1  3  0  1  0  0  0  1  0  0  0  0  3  1  0  0  3  0  3  1  3  3  0  0  0  0  3  1  1  0  0  1  0  1  1  3  3  3  3  3  1  0  0  1  0  0  1  0  0  1  0  0  0  3  0  1  1  1  0  0  3  1  0  0  0  1  0  0  3  0  1  1  3  1  3  1  0  0  3  0  0  3  0  0  1  0  3  3  0  1  3  1  0  1  0  1  3  3  0  1  0  3  3  1  1  1  3  0  1  1  0  3  0  3  1  0  1  0  1  1  0  3  0  1  0  0  3  3  1  1  3  0  0  0  3  1  1  0  0  1  0  1  3  0  1  3  1  0  1  0  0  3  0  1  1  0  0  3  1  3  0  0  3  1  1  1  1  0  1  1  0  1  3  0  0  3  1  3  1  0  3  0  0  0  1  0  1  0  1  1  1  1  3  1  0  0  1  0  0  1  1  1  0  0  3  3  3  3  0  1  3  0  0  0  1  3  1  1  3  1  3  1  0  3  0  1  3  3  1  3  0  0  0  1  1  1  3  3  1  0  1  0  3  0  0  0  3  0  3  0  0  1  0  0  0  0  1  0  1  0  1  3  0  0  1  0  1  0  0  3  0  0  3  1  1  0  0  0  0  3  3  1  1  3  3  0  0  1  0  0  3  0  0  0  3  0  1  1  1  0  3  0  3  0  1  0  0  0  3  1  0  1  0  0  3  0  0  0  1  0  0  0  0  1  1  0  0  0  0  1  0  0  3  1  0  3  0  0  0  0  0  1  1  1  3  1  0  3  3  1  3  1  1  1  0  0  1  0  1  1  0  0  1  0  0  1  0  0  1  0  3  0  0  3  0  0  0  0  0  0  0  0  0  0  1  0  1  1  3  1  1  0  3  0  1  0  0  3  1  3  0  1  3
cell3  1  0  1  0  1  0  0  0  1  3  1  0  1  1  3  1  1  0  0  0  3  3  3  1  3  0  0  3  1  0  3  0  1  1  1  1  1  1  3  1  3  3  3  3  1  1  1  1  1  0  1  0  1  3  1  0  1  0  1  0  3  1  0  1  3  0  3  1  1  3  0  3  1  3  1  0  1  0  1  0  0  1  1  3  1  3  0  1  1  3  1  1  1  3  0  0  0  0  3  3  1  0  0  0  1  0  1  1  0  0  1  1  3  1  1  1  1  1  1  3  3  0  0  1  1  3  3  1  0  1  3  0  0  1  3  0  0  1  0  0  1  1  0  1  3  1  1  3  1  1  3  0  3  3  0  1  0  1  3  1  0  3  1  1  0  1  0  1  1  1  1  1  0  3  1  1  3  1  1  0  3  1  0  0  0  3  1  1  1  3  3  3  1  1  1  0  1  0  0  1  1  1  1  1  1  3  3  1  3  0  1  0  0  1  0  1  0  1  1  0  1  3  0  1  3  0  1  3  0  0  3  0  3  3  3  1  1  1  1  0  0  1  3  1  0  1  0  0  1  0  1  1  0  3  1  3  3  1  0  0  1  1  0  1  1  1  0  1  1  0  0  0  0  3  0  3  0  0  1  0  0  1  1  1  3  1  1  1  1  0  0  1  0  1  0  1  1  1  1  1  1  1  0  1  3  0  1  1  3  1  0  1  1  0  3  1  0  3  1  3  1  1  3  0  1  1  1  1  0  1  3  1  0  0  3  1  0  1  0  1  3  0  1  3  1  1  1  0  1  0  1  0  1  3  3  1  0  1  1  3  0  1  0  3  0  0  3  3  0  1  3  0  0  0  3  0  3  1  1  1  1  0  1  0  1  3  0  1  1  1  0  3  1  3  0  1  0  0  0  3  0  1  0  1  1  1  1  1  1  0  0  1  3  0  0  0  1  1  1  0  1  3  0  3  1  0  1  0  0  3  1  1  1  3  0  3  0  0  1  3  1  1  3  1  1  0  1  3  0  1  1  3  0  1  1  1  1  3  0  0  3  1  0  1  0  1  1  3  1  1  0  0  1  0  0  3  0  0  0  1  3  3  1  3  1  1  1  1  0  3  1  1  0  3  3  1  1  1  1  1
cell4  0  0  3  0  1  0  1  1  3  0  1  0  0  1  0  1  1  0  3  1  3  1  1  1  3  0  0  0  1  1  3  3  3  0  3  1  0  1  0  1  1  1  1  0  0  1  0  0  0  1  0  1  1  0  1  1  0  0  1  1  1  1  0  3  1  1  3  1  3  3  3  1  1  1  3  0  0  0  1  3  1  1  1  1  3  3  1  0  3  1  1  0  1  0  1  1  1  1  1  0  1  1  1  1  3  0  3  0  1  0  1  3  1  1  1  3  1  1  1  0  0  0  1  1  1  3  3  3  0  0  1  0  0  1  1  0  0  3  1  1  1  3  1  1  3  1  0  0  1  3  1  1  1  1  3  0  1  1  1  0  0  3  1  1  1  1  0  3  1  1  0  1  0  3  0  1  1  0  0  0  0  3  1  3  0  0  1  1  3  3  3  0  3  1  3  0  0  1  0  1  1  1  1  1  1  0  1  3  1  0  0  0  1  1  3  1  3  3  1  1  1  0  1  0  1  0  3  1  1  1  1  0  1  3  3  3  1  0  1  0  1  1  0  1  1  0  3  0  0  1  1  1  0  0  1  1  0  3  0  0  1  0  1  1  0  3  1  3  1  1  3  1  0  1  3  1  0  0  0  1  1  1  1  3  3  1  1  1  1  3  1  0  1  1  3  0  0  0  0  3  1  3  1  1  0  0  1  0  1  0  3  3  1  0  1  0  0  0  3  3  0  0  1  1  1  1  3  0  0  0  1  3  0  0  1  1  0  3  0  0  0  3  3  0  0  1  0  1  3  0  3  0  0  1  0  0  0  3  0  3  1  1  1  1  0  0  1  1  3  1  3  0  0  0  1  0  3  1  1  1  1  3  0  0  1  3  0  1  3  3  0  1  3  3  0  1  1  1  1  0  1  0  3  0  3  0  0  1  1  0  3  1  1  0  1  1  0  3  0  1  1  0  1  1  3  1  1  0  0  0  1  0  0  0  3  1  1  0  1  3  1  0  1  0  1  3  1  1  0  1  3  0  1  1  0  1  1  0  1  1  0  3  1  3  1  1  0  1  1  0  3  1  0  1  0  0  0  0  1  0  3  1  1  0  1  3  1  1  1  1  0  3  0  1  0  1  0  0  1  1
cell5  1  1  1  1  1  1  0  0  1  0  1  1  1  1  1  1  1  3  0  3  1  0  0  0  1  3  1  3  3  3  1  0  1  3  3  3  3  0  1  3  1  1  1  1  1  1  0  3  3  0  1  0  1  1  3  0  1  1  1  0  0  0  1  1  0  3  1  1  1  0  1  1  1  1  1  1  1  3  1  0  3  3  3  1  1  3  1  1  0  3  1  3  1  1  1  1  3  1  3  1  1  0  3  0  1  1  1  1  1  0  1  1  0  1  3  1  3  3  1  3  1  1  0  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  0  0  1  1  0  1  0  3  1  3  1  1  0  0  1  3  1  1  0  1  1  3  0  1  0  3  0  1  1  1  1  1  0  1  1  1  3  0  0  1  3  1  1  1  0  0  1  1  3  1  1  1  1  1  1  1  3  0  1  0  1  1  1  3  1  1  0  3  1  1  1  1  1  1  0  1  1  1  1  0  3  3  1  1  0  1  1  3  1  0  1  0  3  1  1  1  1  3  1  1  0  1  0  1  3  3  0  1  3  1  1  0  1  1  1  1  1  3  1  1  1  3  1  3  1  1  1  1  3  1  3  3  3  0  1  1  0  0  1  3  1  3  3  1  1  1  1  1  1  1  3  0  3  1  1  1  3  1  1  1  1  3  1  1  3  3  1  1  1  0  1  1  1  1  1  1  1  1  3  1  1  1  1  1  1  0  1  1  1  1  1  1  1  1  0  1  1  0  1  1  1  3  0  0  1  0  3  1  1  0  1  3  1  1  3  1  0  1  1  1  3  0  3  1  3  1  0  3  3  1  1  1  0  0  0  3  0  1  3  1  1  3  3  0  0  0  3  1  3  3  3  1  1  0  1  1  1  3  0  0  0  3  0  1  1  1  1  1  1  0  1  3  1  1  0  1  0  0  3  1  1  0  1  0  0  3  1  0  1  3  1  1  1  1  3  1  3  3  1  1  1  1  1  1  1  1  1  3  1  1  1  1  1  1  3  3  0  1  1  3  0  1  1  1  0  3  3  1  1  0  0  1  0  3  3  0  1  1  1  1  1  3  1  3  0  1  0  3  1  3  0  1  3  1  3  1  0  1  1  3  1  0
cell6  0  0  3  0  0  3  3  0  1  0  0  0  0  0  1  0  0  0  1  0  0  0  0  0  0  1  0  0  3  0  3  0  3  0  1  0  0  3  3  0  1  3  1  0  3  1  0  0  3  0  1  0  3  0  0  0  0  0  1  0  3  0  1  0  0  1  3  3  0  0  0  1  3  0  1  0  0  1  1  3  0  1  0  3  1  0  1  0  3  1  0  3  0  3  0  0  1  0  1  0  0  3  0  3  1  0  3  0  0  0  0  1  0  0  3  0  1  3  1  1  3  0  0  0  0  0  0  0  0  3  0  3  0  1  3  0  0  0  0  0  0  3  3  3  0  0  3  0  3  0  1  1  1  0  0  3  3  0  1  0  0  0  0  0  0  0  0  3  0  0  0  0  0  3  1  1  0  0  0  0  3  0  0  3  0  0  1  0  0  1  1  3  0  1  0  1  0  0  0  0  0  1  0  0  3  1  0  0  0  0  0  0  0  0  0  1  3  1  1  0  1  3  0  0  1  1  0  1  0  0  3  0  0  1  3  0  1  1  3  0  0  1  0  3  0  1  3  0  0  0  1  0  0  3  1  0  0  0  0  0  0  0  0  3  3  0  0  0  1  0  0  0  3  0  0  0  0  1  0  3  0  1  1  1  0  0  3  0  1  0  0  0  3  3  0  0  0  0  0  0  3  0  1  3  0  0  1  0  0  0  0  0  0  3  1  0  0  0  0  3  3  3  1  0  1  1  0  0  0  3  1  3  0  0  0  1  0  1  0  1  0  0  0  0  0  0  0  3  1  1  0  0  0  1  0  1  0  1  0  3  1  1  0  0  0  0  3  0  1  0  3  3  0  0  3  1  3  0  0  1  1  0  1  0  1  3  0  3  0  1  0  0  0  3  3  0  0  0  0  0  0  1  3  0  1  0  0  3  1  0  0  1  3  0  0  0  0  0  0  0  3  0  0  0  0  0  0  0  0  0  0  3  3  0  3  0  0  0  0  1  3  0  1  0  3  1  1  3  1  1  1  3  0  0  0  0  0  0  0  1  0  0  0  0  3  1  0  0  0  3  3  0  0  0  3  3  0  0  0  0  0  0  0  0  1  1  1  0  0  0  3  3  0  0  0  1  3  0  0  0
cell7  0  0  3  0  3  0  0  1  3  1  0  0  1  0  1  3  1  1  1  1  3  1  1  3  0  0  3  0  1  1  1  1  1  0  1  1  3  1  0  1  1  1  1  0  0  1  1  1  0  1  1  3  0  0  3  1  1  0  1  3  1  1  0  3  1  0  0  1  1  1  1  1  1  1  1  0  0  3  1  3  3  1  3  1  1  3  1  1  1  1  1  3  3  0  3  3  1  0  1  0  1  0  1  1  1  0  0  0  1  1  1  1  1  1  1  0  1  1  1  1  0  0  3  1  1  1  0  0  0  0  1  0  0  1  3  3  0  1  1  1  0  0  1  3  0  1  1  0  0  3  1  1  3  1  1  0  0  1  1  0  1  0  1  3  1  0  0  3  1  3  1  3  3  0  0  1  0  0  0  0  0  1  1  3  3  0  1  3  3  0  3  0  3  1  0  3  0  1  0  1  1  1  1  1  1  1  3  0  3  0  3  1  1  1  0  1  1  3  0  1  0  0  1  0  1  1  1  1  1  1  1  3  0  1  3  0  3  0  1  0  1  1  0  1  0  3  3  0  0  1  1  1  0  0  1  3  0  1  0  0  0  0  1  1  0  3  3  1  1  1  1  1  0  1  3  1  1  3  0  1  3  1  3  3  0  3  3  1  3  1  0  0  1  1  1  0  0  1  3  3  0  3  1  3  0  3  1  0  0  0  3  1  3  0  1  3  3  1  1  0  0  0  1  0  1  0  3  0  0  0  1  1  1  0  1  1  0  1  0  0  0  0  0  1  0  1  0  1  1  0  1  0  3  0  0  3  0  1  0  1  1  1  1  3  1  0  3  1  3  1  1  1  1  0  3  1  0  0  1  1  3  1  3  1  1  1  0  1  0  0  3  1  3  1  0  3  3  0  1  0  1  3  3  0  0  0  3  3  1  0  0  1  3  0  1  1  0  0  0  1  1  0  1  1  0  3  1  0  0  0  1  0  0  0  1  1  0  0  1  3  3  0  1  0  1  1  1  1  1  1  1  1  0  1  0  1  1  3  1  3  1  1  1  3  0  1  0  3  1  0  1  1  3  1  0  0  0  0  0  0  0  3  0  3  1  1  3  1  1  1  0  1  0  1  1  1  0  0  3  3
cell8  1  0  1  3  1  0  0  0  1  0  3  0  1  1  3  3  1  0  0  3  1  0  3  1  1  0  3  3  1  0  0  0  1  1  1  1  1  1  3  1  1  1  1  1  1  3  1  1  1  1  1  0  1  1  1  0  1  1  1  0  0  0  3  1  0  0  3  1  1  0  3  1  0  1  1  0  0  1  1  1  0  1  0  1  1  0  3  1  1  0  1  1  3  0  0  1  3  1  1  0  1  0  1  3  0  0  1  1  1  0  1  1  0  1  1  1  1  3  1  3  3  3  3  3  1  1  1  0  3  3  3  1  0  3  0  0  1  1  3  1  1  1  0  3  0  0  1  3  1  1  0  0  3  3  0  1  3  1  1  1  0  0  1  3  0  1  0  1  1  1  1  3  0  0  1  0  0  1  1  0  1  3  3  0  0  0  1  1  0  0  1  1  1  1  1  0  1  0  0  1  1  1  1  1  0  3  1  0  1  3  1  0  0  1  0  1  3  0  0  0  1  0  1  3  3  1  3  0  0  0  0  0  0  1  0  1  1  1  3  0  1  3  0  1  0  1  3  0  1  0  1  3  3  0  3  3  1  0  0  1  1  3  1  1  0  3  0  1  1  0  0  0  0  1  0  3  0  0  1  0  0  1  3  1  3  1  3  3  3  3  0  1  0  1  0  1  3  1  1  0  0  1  0  3  3  0  3  1  3  1  0  0  1  0  1  1  0  1  1  0  3  1  1  0  3  1  1  1  0  1  1  3  0  0  1  3  0  1  0  3  1  0  1  0  1  0  0  0  0  0  1  0  1  3  0  1  3  3  1  0  0  3  1  1  3  0  0  1  0  1  0  0  0  0  0  0  0  1  1  0  1  3  1  0  1  3  0  0  1  3  0  0  3  1  3  1  3  1  3  0  0  1  0  1  1  0  0  0  3  0  0  1  1  0  0  3  1  1  1  0  1  0  1  0  1  3  1  0  3  1  1  1  1  1  0  0  3  3  1  1  1  0  1  3  1  1  3  1  0  3  1  0  3  3  3  1  1  3  3  1  0  1  3  1  0  3  0  1  0  1  0  0  0  0  0  0  1  0  0  1  3  1  0  3  1  1  1  1  0  1  0  1  0  1  0  1  1  1  1  0
cell9  0  0  0  3  1  0  1  3  3  0  0  3  3  1  3  1  1  0  1  3  0  1  0  1  0  0  0  0  1  1  3  1  1  0  1  1  0  3  0  1  1  1  1  0  3  1  1  0  0  1  1  0  0  3  1  3  3  3  1  1  3  1  0  1  1  1  3  1  0  1  1  1  3  1  1  0  0  1  3  3  1  3  1  3  0  0  1  1  1  1  1  1  1  0  1  1  1  1  1  0  1  1  1  1  1  0  3  0  1  1  1  3  1  1  1  0  1  1  1  0  0  3  1  1  0  1  0  0  1  0  1  0  3  1  1  0  3  1  1  1  1  0  1  1  1  1  1  0  0  0  1  1  1  1  0  0  0  1  3  0  1  3  1  1  1  1  0  3  1  1  1  3  3  0  0  0  1  0  0  3  0  1  1  0  1  0  1  1  1  0  1  3  1  1  0  0  0  1  0  1  1  1  3  1  1  1  1  0  3  0  3  0  0  1  0  1  3  3  1  1  1  0  1  3  1  1  1  1  0  1  1  0  1  0  0  0  1  0  1  0  1  3  1  1  1  0  0  0  0  1  1  1  3  0  1  1  0  0  0  0  0  1  3  1  0  1  1  0  1  1  1  1  0  3  3  1  0  3  0  3  1  1  1  1  0  1  1  1  1  1  0  0  0  3  3  0  3  1  1  3  0  1  3  0  0  0  1  3  0  0  3  1  1  0  1  1  0  1  1  0  3  0  1  1  1  1  3  3  0  0  1  1  1  3  1  1  3  1  0  0  3  0  0  1  3  3  3  1  1  0  0  0  0  3  0  1  3  1  0  1  1  1  1  1  0  0  0  3  0  1  1  3  0  1  1  1  0  1  1  1  3  1  0  0  0  0  0  3  0  0  3  1  1  1  0  1  3  1  1  0  1  1  3  1  0  0  0  1  1  0  0  3  1  0  3  1  0  0  0  1  3  3  3  1  3  1  0  0  0  0  1  3  1  0  1  1  3  3  1  3  1  3  1  1  3  1  1  1  1  1  1  0  1  1  0  1  1  1  1  1  0  1  1  3  1  1  0  0  1  3  1  1  3  1  0  0  0  0  0  0  0  1  1  0  1  3  1  3  1  1  3  1  0  1  0  3  3  3  1  1
cell10  0  0  1  0  1  1  3  0  1  3  1  3  1  3  1  1  1  0  1  0  1  3  0  1  1  3  0  0  3  3  3  0  1  3  3  1  0  1  0  1  3  1  1  0  1  1  1  1  1  0  3  0  0  1  1  3  1  0  1  0  0  0  3  1  3  1  0  1  1  1  1  1  1  1  3  0  0  1  3  1  3  3  1  1  1  1  1  1  0  1  1  1  1  1  3  1  3  1  1  3  1  0  3  0  1  0  1  1  1  0  1  1  0  1  1  1  1  1  3  1  0  0  0  0  1  3  1  0  3  1  1  0  0  1  0  0  1  1  0  0  1  3  0  1  0  0  1  1  1  1  0  0  1  3  1  1  0  3  3  1  3  0  1  0  0  1  0  1  1  1  1  0  0  3  1  1  3  0  1  3  1  3  0  0  1  0  1  1  1  0  1  1  3  1  1  3  0  0  0  1  0  1  3  1  3  1  0  0  1  0  1  0  0  1  0  1  3  3  1  0  1  0  0  1  1  1  1  3  3  0  0  0  1  1  0  3  1  1  3  0  0  3  1  3  0  1  0  1  1  0  1  1  0  3  0  1  1  0  3  1  1  1  1  1  1  3  0  1  3  0  0  0  0  1  1  0  1  0  1  0  0  0  1  1  0  3  3  3  0  3  0  1  0  0  0  0  1  3  0  0  1  3  3  1  1  0  1  1  0  1  3  1  1  0  1  1  0  1  1  3  1  1  3  0  1  1  1  1  0  1  1  1  0  0  1  1  0  3  0  1  0  0  1  0  1  1  0  1  1  0  1  0  3  1  3  1  0  1  1  0  1  1  3  1  0  0  0  0  3  1  3  0  0  0  0  0  0  1  1  3  1  0  1  3  1  1  0  1  1  1  0  0  1  1  0  1  0  0  0  0  3  1  0  1  1  0  1  0  3  0  1  0  0  0  0  0  1  3  1  0  1  3  0  1  1  0  1  0  0  3  3  1  1  0  0  0  0  0  1  1  1  3  1  1  1  1  3  3  1  1  1  0  0  1  1  1  1  0  3  1  0  1  1  1  3  3  1  0  0  1  0  0  3  0  0  0  0  3  0  3  1  1  0  0  1  1  1  0  0  1  1  1  0  1  0  1  1  3  1  0
cell11  0  0  1  0  1  0  1  1  1  0  0  0  1  0  1  1  1  0  1  1  0  1  1  1  3  1  0  0  1  1  3  3  1  0  1  3  0  1  0  3  1  1  1  0  0  1  1  3  0  1  1  1  0  0  1  3  1  0  0  1  1  1  0  1  3  1  3  1  0  3  1  0  3  1  1  3  0  1  0  1  1  0  3  1  1  0  1  1  3  1  1  3  1  0  1  1  1  1  1  0  1  1  1  1  1  0  3  0  1  1  1  1  1  1  1  0  1  3  1  0  0  0  1  0  1  1  0  0  3  0  1  0  0  1  3  1  0  1  3  1  1  0  1  1  0  3  1  0  3  1  1  1  1  1  3  3  1  1  1  0  1  1  1  1  3  1  0  1  3  1  3  1  0  0  0  1  1  0  0  0  0  1  1  0  1  3  1  1  1  0  0  0  1  3  0  0  1  1  0  1  0  1  1  0  3  1  3  0  1  3  3  3  3  1  3  3  1  1  1  1  0  3  1  0  1  0  1  3  1  1  3  3  1  3  3  3  1  0  1  0  1  1  0  1  1  1  0  0  0  1  3  1  0  1  1  1  0  0  0  0  1  0  3  1  0  1  1  0  0  1  3  1  0  1  1  1  0  0  0  1  1  1  3  1  0  1  1  1  3  1  0  0  0  1  1  0  0  0  1  0  3  1  1  0  0  0  1  3  0  0  0  0  1  3  1  0  0  1  1  0  0  0  3  1  0  1  1  0  0  0  3  0  1  3  0  1  3  1  3  0  3  0  0  1  0  1  0  3  3  0  0  0  0  1  0  3  0  1  0  1  0  3  1  1  3  3  3  1  3  1  1  3  1  3  1  0  0  0  1  1  1  3  0  0  1  0  3  0  0  0  3  3  0  1  0  0  1  3  1  0  1  1  0  3  1  0  0  1  1  0  0  1  1  0  1  3  3  0  3  3  3  0  1  1  3  3  1  0  0  0  1  0  0  0  1  0  1  1  1  1  3  0  1  0  3  1  1  0  3  3  1  0  1  3  3  1  1  3  1  1  0  1  1  0  1  0  0  3  0  3  1  3  0  1  0  0  0  3  0  3  0  3  1  0  3  1  3  1  1  1  3  1  3  3  3  1  0  3  1  1
cell12  1  0  3  0  0  0  0  0  1  0  0  0  0  0  1  0  0  0  1  0  0  3  3  0  0  0  3  0  0  0  0  0  0  3  1  0  0  0  0  0  1  0  1  0  0  1  0  0  3  0  0  3  0  0  1  0  3  0  1  3  1  0  0  0  3  3  1  3  0  0  0  1  1  0  1  3  0  3  3  3  3  3  0  1  3  0  1  0  3  0  3  0  0  0  0  0  1  1  0  1  3  0  0  1  1  3  1  1  0  3  0  1  0  0  1  0  1  1  1  3  3  0  3  3  0  0  0  0  0  0  3  1  0  0  1  0  0  1  0  0  3  0  0  0  0  1  1  1  3  0  0  0  0  3  0  1  0  0  1  0  0  0  0  0  0  1  3  0  0  0  0  1  0  0  0  1  0  0  0  0  3  0  0  0  0  0  1  0  0  3  1  3  0  1  0  0  0  0  1  0  3  3  0  0  3  0  0  0  3  0  3  0  0  3  0  1  1  0  1  0  1  3  0  0  3  0  3  0  0  3  0  0  1  1  0  0  1  0  1  0  0  1  3  3  0  3  0  0  0  0  3  0  0  0  3  0  0  0  0  3  0  0  0  0  0  0  3  0  0  0  0  0  0  0  0  0  3  3  0  0  0  1  3  1  0  0  3  0  1  0  1  0  0  3  0  0  0  1  3  0  3  3  0  0  0  0  1  0  0  0  1  3  3  0  3  0  0  0  0  0  0  0  0  0  1  1  0  0  0  0  0  1  0  0  1  1  0  1  0  3  0  0  0  0  3  0  0  3  1  0  3  0  0  1  0  1  3  1  0  0  0  3  0  0  0  0  1  1  1  0  0  3  0  0  0  3  0  3  0  0  3  1  3  0  1  0  0  1  0  0  0  0  1  1  3  0  0  3  0  0  0  1  0  0  0  3  0  0  1  0  3  1  0  3  0  0  0  0  0  0  1  0  0  0  3  0  3  0  0  0  0  3  0  0  0  0  3  0  3  1  0  0  0  0  0  1  1  1  1  1  1  3  0  0  1  0  0  3  0  3  3  0  1  1  3  1  3  0  0  3  0  1  3  0  3  3  0  0  3  0  0  0  0  3  1  1  3  0  0  0  0  0  0  0  0  1  0  0  0  0
cell13  0  0  1  0  1  0  3  1  1  0  3  1  3  1  1  1  1  0  1  3  3  1  1  1  0  0  0  0  3  1  1  1  1  0  1  1  0  1  3  3  3  1  3  1  0  1  1  0  3  3  1  3  0  1  1  1  1  0  1  3  1  1  3  1  3  1  0  1  0  1  1  3  1  1  1  0  3  1  3  1  1  1  1  1  1  0  3  3  1  3  3  1  1  0  1  0  1  1  1  0  1  1  1  1  0  3  0  0  1  0  1  1  1  1  1  3  3  3  1  0  0  0  3  1  3  1  0  0  0  0  3  0  0  1  1  3  0  3  1  3  1  3  1  1  1  1  1  1  3  0  1  1  1  1  0  0  3  1  1  0  3  0  1  1  0  1  0  1  1  1  3  1  0  0  0  1  0  0  0  3  3  1  3  3  1  1  1  3  1  0  3  0  3  1  0  0  0  1  0  1  1  1  3  3  1  0  1  0  1  3  0  3  1  3  0  1  1  1  1  1  1  3  1  0  1  1  1  1  1  1  1  1  1  3  0  0  1  0  1  3  1  1  0  1  1  1  0  0  1  1  1  1  0  3  1  3  1  3  0  3  3  0  1  1  0  1  0  0  3  1  3  1  3  3  3  1  3  0  0  0  0  1  3  0  0  1  1  1  1  1  0  0  0  3  1  0  0  1  1  0  0  1  1  0  0  0  3  3  0  0  0  1  1  0  1  0  0  3  1  0  0  0  1  1  1  1  1  0  3  3  1  1  1  3  1  1  0  1  0  0  3  3  3  1  0  1  0  1  3  0  0  3  0  1  0  3  0  0  0  3  1  1  1  0  1  0  3  1  0  1  1  1  3  1  0  3  0  1  0  0  1  1  0  0  1  0  0  1  0  3  1  1  0  0  0  0  3  3  1  0  1  1  0  3  0  0  3  3  3  0  0  1  3  3  1  3  0  3  0  1  1  3  1  0  3  1  3  0  0  0  3  0  3  0  0  1  1  3  1  1  0  0  1  0  1  1  1  1  3  3  1  0  3  3  0  1  1  1  1  3  0  1  1  0  1  1  0  1  0  0  1  1  1  3  3  0  0  1  0  0  1  3  1  1  1  3  1  3  1  1  3  1  0  1  0  1  0  3  1  1
cell14  0  3  3  0  1  0  0  0  1  0  0  0  0  3  0  0  0  0  3  0  0  0  0  1  0  3  0  0  3  0  0  3  1  0  1  0  0  0  0  1  3  0  1  3  0  1  0  0  0  0  0  1  0  0  1  0  0  0  1  0  0  0  0  0  1  0  0  0  0  3  0  1  1  0  1  3  3  1  1  1  0  0  0  0  1  0  1  0  0  1  0  0  3  1  0  0  0  3  1  0  1  0  0  0  1  0  0  1  0  0  1  1  0  3  3  1  3  1  1  3  0  3  1  0  0  0  0  1  0  0  0  3  0  1  0  3  0  1  0  0  0  3  0  0  0  0  3  0  0  0  3  0  0  0  3  0  0  0  3  0  0  0  0  0  0  0  0  3  1  0  3  0  0  0  0  1  0  0  3  0  1  0  0  0  0  0  1  3  3  3  1  1  3  1  3  0  3  0  0  0  0  1  0  0  3  1  0  0  0  0  0  1  0  3  1  1  3  0  0  0  1  1  0  0  1  0  3  0  0  0  0  3  0  1  0  0  1  0  3  0  3  1  3  0  0  1  0  0  0  0  1  1  0  0  1  0  0  0  0  1  0  1  0  0  3  0  0  0  1  3  0  0  3  0  0  0  0  3  0  0  0  1  3  1  1  0  0  0  3  0  0  0  0  3  3  0  3  1  1  0  0  0  0  0  0  0  1  0  0  3  0  0  0  0  1  0  1  0  3  0  0  0  0  0  1  1  0  3  0  0  0  1  0  0  1  3  0  1  0  3  3  0  0  3  0  0  0  3  1  0  0  0  0  1  3  1  0  3  0  3  0  3  0  3  1  3  0  0  0  0  0  0  0  1  3  0  0  3  1  0  1  0  3  0  1  0  0  3  0  0  1  0  0  0  3  3  0  0  0  3  1  1  0  3  0  0  0  0  1  0  3  1  3  0  3  0  0  1  0  0  1  3  3  0  0  1  3  0  0  0  3  0  3  0  3  0  0  0  3  1  1  0  0  0  0  1  1  3  1  1  1  0  0  0  0  0  0  0  0  3  0  0  3  3  1  1  1  1  0  0  0  0  0  0  1  3  0  3  0  3  0  3  1  3  0  3  1  0  0  0  3  0  0  3  0  1  0  0  0  3
cell15  0  3  1  0  3  1  1  1  1  3  1  0  3  1  3  3  3  0  1  1  0  3  1  0  0  0  3  0  1  1  1  3  1  0  1  1  3  1  0  1  1  1  1  0  0  3  1  0  0  1  1  1  3  3  1  1  1  0  3  3  3  0  0  1  1  1  0  1  0  1  1  1  1  1  1  0  0  1  1  1  1  1  1  0  1  0  1  3  1  1  1  1  1  3  1  3  0  3  1  0  1  1  1  1  3  0  0  0  1  3  1  1  1  1  1  3  1  3  1  0  0  0  1  3  1  1  1  3  0  0  1  3  0  1  0  0  0  1  1  1  3  0  1  1  1  1  1  0  1  0  1  3  0  1  0  3  1  1  1  1  1  0  1  1  1  3  0  1  1  1  1  1  0  0  0  1  1  0  0  0  3  3  1  1  3  0  1  1  1  0  1  0  1  1  3  0  1  1  0  3  1  1  3  3  1  0  1  3  1  0  0  0  1  1  0  3  3  1  1  1  1  0  1  0  3  3  1  1  1  1  1  3  3  3  0  1  1  0  0  0  1  1  0  1  1  0  0  0  0  3  1  1  0  3  1  1  0  0  0  0  1  0  0  1  0  0  1  0  1  1  1  1  0  1  3  1  1  3  0  1  1  1  3  1  0  1  3  1  3  1  3  0  0  3  1  0  0  3  1  1  3  1  0  3  0  0  1  1  0  0  0  1  3  0  1  0  3  1  1  0  0  0  1  1  3  1  1  0  0  0  1  3  1  0  1  3  1  3  3  1  0  0  3  1  0  1  0  1  0  0  0  0  0  1  0  3  3  1  0  1  1  0  1  1  0  3  3  1  0  1  1  1  1  0  1  0  0  1  1  3  1  1  0  0  1  3  3  3  3  0  0  3  0  1  0  1  1  1  0  0  1  1  0  0  3  0  0  1  3  3  0  1  1  1  3  0  0  1  0  1  3  0  1  1  0  1  1  0  0  3  1  0  1  1  3  1  1  1  3  1  3  0  1  0  1  1  1  0  1  1  1  0  1  1  0  1  1  1  1  1  0  3  1  0  3  1  0  1  1  0  3  1  0  1  0  0  1  0  0  0  0  3  3  1  1  1  1  1  0  1  0  0  0  1  1  3  3  0  1  3
cell16  1  0  3  0  1  0  0  1  3  0  3  0  1  1  3  3  1  0  3  0  1  1  1  1  3  0  3  0  1  0  1  1  1  1  1  1  1  0  3  1  1  1  0  3  0  3  1  1  1  0  1  0  0  1  3  0  1  1  1  0  1  0  1  3  3  0  0  1  3  0  1  1  1  1  3  0  0  1  1  1  0  1  1  0  1  1  1  1  0  1  1  1  1  0  0  1  0  1  1  0  1  0  1  0  1  0  1  1  0  0  1  0  0  1  3  1  1  3  1  3  1  0  0  1  1  1  3  0  0  1  1  3  0  0  3  0  0  1  0  0  1  0  1  1  1  3  1  0  1  3  3  0  1  1  0  1  3  1  0  1  0  0  0  3  3  3  0  1  1  1  1  1  0  3  0  1  3  0  3  0  1  1  0  0  3  0  0  1  1  3  1  1  3  1  1  0  1  3  0  1  1  1  1  1  0  3  3  3  3  0  1  0  3  1  0  1  3  1  3  0  1  0  0  1  1  1  1  0  0  0  0  0  1  1  0  1  1  1  1  3  0  1  1  3  3  1  1  3  1  0  1  1  1  0  1  1  1  0  0  1  3  1  1  3  1  1  3  1  3  0  0  0  3  1  0  3  1  0  1  0  0  1  3  1  0  1  0  1  1  0  0  1  1  0  0  1  3  3  1  0  1  0  3  1  0  0  1  1  3  1  1  1  0  0  1  1  0  1  3  3  1  1  1  3  1  0  1  0  3  1  1  1  0  0  1  1  1  1  3  1  0  0  1  0  1  1  3  3  1  3  0  3  1  3  1  1  0  1  3  0  0  3  0  1  0  0  3  1  0  1  3  0  3  0  3  3  3  1  1  0  3  0  3  0  3  1  1  0  1  0  0  0  1  3  0  1  0  3  0  0  0  0  0  1  1  0  3  3  1  3  1  1  0  0  0  0  1  1  3  3  3  1  1  0  1  0  1  0  0  1  1  1  1  0  3  0  0  3  1  1  1  1  1  1  1  3  1  1  3  1  1  3  0  1  1  1  1  0  0  1  3  1  3  1  0  1  1  3  0  1  0  3  1  0  0  0  0  0  3  0  1  1  0  1  1  0  0  1  0  1  0  3  3  1  0  1  0  3  1  3
cell17  0  0  1  1  0  0  0  0  0  0  3  0  1  0  3  0  3  0  0  0  0  3  0  3  0  3  0  0  3  0  0  0  3  0  1  3  0  0  0  0  1  3  3  1  0  1  0  0  0  0  1  0  0  0  3  0  3  0  1  3  1  3  0  0  0  3  0  0  0  0  3  1  1  0  1  0  0  1  1  1  0  0  0  3  1  1  1  0  0  1  3  3  0  0  3  0  1  3  3  0  0  0  3  0  1  0  3  0  0  3  1  1  0  3  0  0  0  1  3  0  0  0  0  3  0  0  0  0  0  0  3  0  0  1  3  0  0  1  0  0  1  1  1  0  0  0  0  0  0  0  0  0  3  0  3  0  0  0  1  0  0  0  0  0  0  0  0  0  0  3  0  0  0  0  0  1  0  0  0  3  3  0  0  3  0  3  3  0  0  0  1  0  0  1  0  0  0  0  0  3  0  3  3  0  0  1  0  0  0  3  0  0  0  0  3  3  0  0  3  3  1  0  3  3  1  0  3  0  3  3  0  3  3  1  0  1  3  0  1  0  3  3  0  3  3  1  0  1  0  0  1  1  3  0  3  0  0  0  0  3  0  0  0  0  0  0  0  0  3  0  3  3  0  1  0  0  0  0  3  3  0  1  0  1  0  0  0  0  1  3  0  3  0  0  0  0  3  1  1  0  0  0  0  0  3  3  1  0  0  1  0  0  3  0  3  0  0  0  0  1  0  0  0  0  1  1  0  1  3  0  0  1  0  3  1  1  0  1  0  0  0  1  0  0  0  0  0  3  1  3  0  0  0  1  3  0  0  1  1  0  3  3  0  0  0  0  0  0  0  0  0  0  0  0  0  0  0  0  3  3  1  0  0  0  3  3  0  1  0  0  0  0  3  1  0  0  3  0  1  0  0  1  0  0  0  0  0  0  1  0  1  1  3  0  0  3  0  1  0  0  1  3  3  0  0  0  3  3  0  0  3  0  0  0  0  3  0  0  3  1  0  0  0  1  0  1  0  3  1  1  0  0  3  0  0  0  0  1  0  3  0  0  3  0  3  1  3  0  0  0  0  0  0  0  0  0  0  0  1  0  0  0  0  0  3  3  1  3  0  0  0  0  3  1  0  3  0  1  0  3
cell18  0  0  3  3  1  0  0  0  0  0  1  0  1  1  1  1  1  0  0  3  1  0  0  1  3  0  0  0  1  0  1  1  1  0  0  0  0  1  0  1  1  1  1  0  0  1  1  1  3  1  1  0  0  0  3  3  3  0  1  0  1  0  0  1  0  0  3  1  0  0  1  1  1  1  1  0  0  3  1  1  0  3  1  0  0  3  1  1  0  1  1  1  3  3  1  1  1  3  3  0  0  0  1  3  1  3  0  1  1  0  1  1  3  3  3  0  1  1  1  0  3  0  0  1  1  1  0  1  3  1  1  0  0  1  0  0  0  1  3  0  1  0  0  3  0  0  1  0  3  0  0  0  1  1  0  3  0  1  1  3  0  0  1  0  0  0  0  3  1  1  1  1  0  0  0  1  0  3  0  0  0  1  0  0  3  0  3  3  1  0  1  0  3  1  0  3  0  0  1  1  1  1  1  1  3  1  3  0  3  3  0  1  3  3  0  1  1  3  1  0  1  1  0  0  1  1  0  0  3  0  0  0  1  1  0  0  0  0  1  0  0  1  0  3  0  1  0  0  0  0  1  1  1  0  0  3  0  0  3  3  3  3  1  1  3  0  0  3  1  0  0  0  0  1  0  0  0  1  0  0  0  1  1  1  0  0  1  1  1  1  0  0  0  0  3  3  1  3  1  0  1  0  0  0  0  0  1  0  0  0  0  1  1  0  1  0  3  1  3  0  0  3  1  0  1  1  1  0  0  0  1  1  3  0  1  0  3  1  0  0  0  0  0  0  3  0  0  0  3  0  0  0  3  1  0  1  3  1  3  0  0  1  0  1  1  0  0  3  0  1  3  1  1  3  1  3  3  1  1  3  1  0  1  0  3  0  0  1  0  0  0  0  0  1  0  1  0  0  0  0  0  1  3  3  0  3  3  0  1  1  0  3  0  0  0  0  0  0  3  0  1  0  1  0  0  0  1  0  0  0  1  1  0  0  0  0  3  0  1  1  1  0  3  0  1  1  1  1  1  3  1  0  0  3  0  3  1  3  0  3  0  3  1  0  1  3  0  0  0  0  0  0  0  0  0  0  0  3  0  0  3  1  0  1  1  1  3  1  0  3  0  1  0  1  0  1  0  0  1  0

而CNV格式较为简单，即为整数，如下：

chr  start  end  width  SA501X3F-00015  SA501X3F-00003  SA501X3F-00153  SA501X3F-00114  SA501X3F-00058  SA501X3F-00016  SA501X3F-00038  SA501X3F-00071  SA501X3F-00090  SA501X3F-00142  SA501X3F-00079  SA501X3F-00140  SA501X3F-00059  SA501X3F-00111  SA501X3F-00161  SA501X3F-00182  SA501X3F-00151  SA501X3F-00143  SA501X3F-00093  SA501X3F-00033  SA501X3F-00092  SA501X3F-00037  SA501X3F-00027  SA501X3F-00056  SA501X3F-00094  SA501X3F-00005  SA501X3F-00156  SA501X3F-00132  SA501X3F-00177  SA501X3F-00187  SA501X3F-00054  SA501X3F-00162  SA501X3F-00021  SA501X3F-00127  SA501X3F-00062  SA501X3F-00023  SA501X3F-00082  SA501X3F-00166  SA501X3F-00063  SA501X3F-00145  SA501X3F-00010  SA501X3F-00103  SA501X3F-00117  SA501X3F-00168  SA501X3F-00116  SA501X3F-00107  SA501X3F-00098  SA501X3F-00164  SA501X3F-00184  SA501X3F-00042  SA501X3F-00138  SA501X3F-00080  SA501X3F-00115  SA501X3F-00018  SA501X3F-00189  SA501X3F-00008  SA501X3F-00035  SA501X3F-00013  SA501X3F-00067  SA501X3F-00119  SA501X3F-00118  SA501X3F-00069  SA501X3F-00057  SA501X3F-00043  SA501X3F-00050  SA501X3F-00083  SA501X3F-00030  SA501X3F-00190  SA501X3F-00147  SA501X3F-00020  SA501X3F-00167  SA501X3F-00040  SA501X3F-00019  SA501X3F-00065  SA501X3F-00188  SA501X3F-00186  SA501X3F-00046  SA501X3F-00112  SA501X3F-00169  SA501X3F-00014  SA501X3F-00109  SA501X3F-00128  SA501X3F-00165  SA501X3F-00133  SA501X3F-00150  SA501X3F-00097  SA501X3F-00028  SA501X3F-00157  SA501X3F-00171  SA501X3F-00122  SA501X3F-00032  SA501X3F-00086  SA501X3F-00155  SA501X3F-00185  SA501X3F-00039  SA501X3F-00105  SA501X3F-00131  SA501X3F-00026  SA501X3F-00181  SA501X3F-00024  SA501X3F-00121  SA501X3F-00152  SA501X3F-00077  SA501X3F-00102  SA501X3F-00110  SA501X3F-00130  SA501X3F-00172  SA501X3F-00183  SA501X3F-00070  SA501X3F-00148  SA501X3F-00034  SA501X3F-00100  SA501X3F-00036  SA501X3F-00004  SA501X3F-00136  SA501X3F-00049  SA501X3F-00170  SA501X3F-00011  SA501X3F-00060  SA501X3F-00087  SA501X3F-00064  SA501X3F-00031  SA501X3F-00160  SA501X3F-00123  SA501X3F-00108  SA501X3F-00343  SA501X3F-00266  SA501X3F-00347  SA501X3F-00380  SA501X3F-00337  SA501X3F-00363  SA501X3F-00257  SA501X3F-00375  SA501X3F-00290  SA501X3F-00349  SA501X3F-00255  SA501X3F-00212  SA501X3F-00259  SA501X3F-00195  SA501X3F-00268  SA501X3F-00322  SA501X3F-00310  SA501X3F-00286  SA501X3F-00219  SA501X3F-00305  SA501X3F-00315  SA501X3F-00382  SA501X3F-00362  SA501X3F-00239  SA501X3F-00374  SA501X3F-00321  SA501X3F-00236  SA501X3F-00201  SA501X3F-00378  SA501X3F-00299  SA501X3F-00365  SA501X3F-00308  SA501X3F-00282  SA501X3F-00277  SA501X3F-00373  SA501X3F-00205  SA501X3F-00358  SA501X3F-00245  SA501X3F-00301  SA501X3F-00213  SA501X3F-00292  SA501X3F-00350  SA501X3F-00222  SA501X3F-00231  SA501X3F-00303  SA501X3F-00368  SA501X3F-00317  SA501X3F-00320  SA501X3F-00216  SA501X3F-00230  SA501X3F-00223  SA501X3F-00338  SA501X3F-00353  SA501X3F-00294  SA501X3F-00326  SA501X3F-00371  SA501X3F-00262  SA501X3F-00210  SA501X3F-00252  SA501X3F-00366  SA501X3F-00381  SA501X3F-00341  SA501X3F-00348  SA501X3F-00258  SA501X3F-00318  SA501X3F-00208  SA501X3F-00248  SA501X3F-00377  SA501X3F-00265  SA501X3F-00207  SA501X3F-00352  SA501X3F-00333  SA501X3F-00300  SA501X3F-00316  SA501X3F-00346  SA501X3F-00281  SA501X3F-00295  SA501X3F-00235  SA501X3F-00291  SA501X3F-00194  SA501X3F-00256  SA501X3F-00331  SA501X3F-00228  SA501X3F-00345  SA501X3F-00199  SA501X3F-00323  SA501X3F-00360  SA501X3F-00355  SA501X3F-00344  SA501X3F-00224  SA501X3F-00204  SA501X3F-00250  SA501X3F-00324  SA501X3F-00339  SA501X3F-00314  SA501X3F-00376  SA501X3F-00227  SA501X3F-00269  SA501X3F-00356  SA501X3F-00251  SA501X3F-00335  SA501X3F-00220  SA501X3F-00243  SA501X3F-00233  SA501X3F-00361  SA501X3F-00237  SA501X3F-00253  SA501X3F-00244  SA501X3F-00270  SA501X3F-00325  SA501X3F-00221  SA501X3F-00357  SA501X3F-00311  SA501X3F-00214  SA501X3F-00351  SA501X3F-00267  SA501X3F-00232  SA501X3F-00297  SA501X3F-00302  SA501X3F-00274  SA501X3F-00246  SA501X3F-00264  SA501X3F-00298  SA501X3F-00209  SA501X3F-00275  SA501X3F-00198  SA501X3F-00215  SA501X3F-00226  SA501X3F-00328  SA501X3F-00370  SA501X3F-00296  SA501X3F-00193  SA501X3F-00289  SA501X3F-00306  SA501X3F-00359
1  1  150000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1
1  150001  300000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1
1  300001  450000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1
1  450001  600000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1
1  600001  750000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1
1  750001  900000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1
1  900001  1050000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1
1  1050001  1200000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1
1  1200001  1350000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1
1  1350001  1500000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1
1  1500001  1650000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1
1  1650001  1800000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1
1  1800001  1950000  150000  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  2  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1  1

关于运行问题

该软件包运行主要分两个步骤：

运行 MATLAB脚本文件，名为"carryout_RPCA.m" 生成基因型矩阵；
运行R 语言脚本文件，名为 “carryout_clonal_tree.R” 对细胞进行聚类并且重构克隆进化树。

其中carryout_clonal_tree.R运行需要改一下路径以及一些命名问题，如下：

setwd('./RobustClone/example')
source('./RobustClone/matlab_and_R_scripts/Clustering_EvolutionaryTree_function.R')

## example for SNV data
AA1_example <- R.matlab:::readMat('example_RobustClone.mat')
AA <- AA1_example[[1]] # Read GTM recovered by RPCA model or extended RPCA model 

robust_clone <- LJClustering(AA) # Louvain-Jaccard clustering
clone_gety <- subclone_GTM(AA, robust_clone, 'SNV') # obtain subclonal GTM
MST <- plot_MST(clone_gety, robust_clone, 'SNV', 'exampledata') # calculate and plot clonal MST
clones_mt <- new_variant_site(clone_gety, MST, 'SNV') # obtain the variant SNV loci each subclone compared with its parent subclone


## example for CNV data
AA1_example <- R.matlab:::readMat('SA501X3F_RobustClone.mat')
AA <- AA1_example[[1]] # Read copy number profiles recovered by RPCA model or extended RPCA model 

robust_clone <- LJClustering(AA) # Louvain-Jaccard clustering
clone_gety <- subclone_GTM(AA, robust_clone, 'CNV') # obtain subclonal copy number profiles
MST <- plot_MST(clone_gety, robust_clone, 'CNV', 'exampledata') # calculate and plot clonal MST
clones_vt <- new_variant_site(clone_gety, MST, 'CNV', 'parent') # obtain the CNV genome fragments of each subclone compared with its parent subclone or normal cell

data_info <- read.csv('SA501X3F.integer_copy_number.csv',header = TRUE) # the chromosome and copy number profiles information of SA501X3F data
chr <- data_info$chr # the chromosomes in which each genome fragment is located

clones_change_chr <- clonal_CNV_chr(clones_vt, chr) # obtain the variant chromosomes in which all genome fragments with CNV in clones_vt variable are located
clones_vt_state <- new_CNV_chr_state(clone_gety, MST, chr, clones_change_chr, 'parent') # get the statistical frequency of how many copy number of each genome segment have changed for each chromosome and chromosome states when compared to parent subclone or normal cell or the root/first subclone of evolutionary tree

关于结果解读

该软件包给出例子结果，如下：

文章中使用真实数据进行测试，数据来源于高级别浆液性卵巢癌数据集 HGSOC，该数据包括 420 细胞和 43 SNV 其中10%多缺失。

利用 RobustClone 去噪前后对比的热图，如下：

利用 RobustClone 重构的克隆进化树，同时重构的进化树中包含的 HGSOC 数据的重叠细胞数，以及由 SCG 识别的克隆中包含的细胞数，如下：

RobustClone 在算法上同其他四款软件进行比较，包括 SCG，BEAM，SCITE 和 SiFit，后期如果时间允许我们也将在公众号进行解读，敬请关注！
在这里插入图片描述

Reference：

Ziwei Chen, Fuzhou Gong, Lin Wan, Liang Ma, RobustClone: a robust PCA method for tumor clone and evolution inference from single-cell sequencing data, Bioinformatics, Volume 36, Issue 11, June 2020, Pages 3299–3306.
McPherson A, Roth A, Laks E, et al. Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer. Nat Genet. 2016;48(7):758-767.