XenofilteR: computational deconvolution of mouse and human reads in tumor xenograft sequence data.
XenofilteR: computational deconvolution of mouse and human reads in tumor xenograft sequence data.
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DOI：
10.1186/s12859-018-2353-5
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发表时间：
2018-10-04
影响因子：
3
通讯作者：
Krijgsman O
中科院分区：
文献类型：
--
作者：
Kluin RJC;Kemper K;Kuilman T;de Ruiter JR;Iyer V;Forment JV;Cornelissen-Steijger P;de Rink I;Ter Brugge P;Song JY;Klarenbeek S;McDermott U;Jonkers J;Velds A;Adams DJ;Peeper DS;Krijgsman O
来自（患者源性）肿瘤（PDX）或肿瘤细胞系的小鼠异种移植物被广泛用作研究癌症的各种生物学和临床前方面的模型。然而，分析它们的RNA和DNA谱是具有挑战性的，因为它们不仅包含来自移植的人类癌症的读取，还包括来自小鼠宿主的读取。小鼠来源的读数导致DNA样本突变分析的假阳性，并且在测序RNA时模糊基因表达水平。然而，目前可用的算法是有限的，精度和易用性的改进是必要的。我们开发了R-package xenfilter，它可以根据序列reads和参考基因组之间的编辑距离将小鼠和人类序列reads分开。为了评估xenfilter的准确性，我们通过计算机混合小鼠和人类DNA序列数据来生成序列数据。这些分析表明，xenfilter在保留人类序列的同时，去除了99.9%的小鼠序列。这使得异种移植物样本的突变分析具有准确的变异等位基因频率，并检索所有非同义体细胞肿瘤突变。xenfilter准确地解剖来自小鼠和人类的RNA和DNA序列，从而优于目前可用的工具。xenfilter是开源的，可以在https://github.com/PeeperLab/XenofilteR上获得。本文的在线版本（10.1186/s12859-018-2353-5）包含补充内容，仅供授权用户使用。
Mouse xenografts from (patient-derived) tumors (PDX) or tumor cell lines are widely used as models to study various biological and preclinical aspects of cancer. However, analyses of their RNA and DNA profiles are challenging, because they comprise reads not only from the grafted human cancer but also from the murine host. The reads of murine origin result in false positives in mutation analysis of DNA samples and obscure gene expression levels when sequencing RNA. However, currently available algorithms are limited and improvements in accuracy and ease of use are necessary. We developed the R-package XenofilteR, which separates mouse from human sequence reads based on the edit-distance between a sequence read and reference genome. To assess the accuracy of XenofilteR, we generated sequence data by in silico mixing of mouse and human DNA sequence data. These analyses revealed that XenofilteR removes > 99.9% of sequence reads of mouse origin while retaining human sequences. This allowed for mutation analysis of xenograft samples with accurate variant allele frequencies, and retrieved all non-synonymous somatic tumor mutations. XenofilteR accurately dissects RNA and DNA sequences from mouse and human origin, thereby outperforming currently available tools. XenofilteR is open source and available at https://github.com/PeeperLab/XenofilteR. The online version of this article (10.1186/s12859-018-2353-5) contains supplementary material, which is available to authorized users.
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影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
影响因子：
82.9
作者：
Gao, Hui;Korn, Joshua M.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
46.9
作者：
Trapnell C;Williams BA;Pertea G;Mortazavi A;Kwan G;van Baren MJ;Salzberg SL;Wold BJ;Pachter L
通讯作者：
Pachter L
影响因子：
64.8
作者：
Stewart E;Federico SM;Chen X;Shelat AA;Bradley C;Gordon B;Karlstrom A;Twarog NR;Clay MR;Bahrami A;Freeman BB 3rd;Xu B;Zhou X;Wu J;Honnell V;Ocarz M;Blankenship K;Dapper J;Mardis ER;Wilson RK;Downing J;Zhang J;Easton J;Pappo A;Dyer MA
通讯作者：
Dyer MA
影响因子：
8.8
作者：
Kemper K;Krijgsman O;Kong X;Cornelissen-Steijger P;Shahrabi A;Weeber F;van der Velden DL;Bleijerveld OB;Kuilman T;Kluin RJC;Sun C;Voest EE;Ju YS;Schumacher TNM;Altelaar AFM;McDermott U;Adams DJ;Blank CU;Haanen JB;Peeper DS
通讯作者：
Peeper DS