Comparing the utility of in vivo transposon mutagenesis approaches in yeast species to infer gene essentiality.
Comparing the utility of in vivo transposon mutagenesis approaches in yeast species to infer gene essentiality.
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DOI：
10.1007/s00294-020-01096-6
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发表时间：
2020-12
期刊：
影响因子：
2.5
通讯作者：
Berman J
中科院分区：
文献类型：
--
作者：
Levitan A;Gale AN;Dallon EK;Kozan DW;Cunningham KW;Sharan R;Berman J
体内转座子诱变，加上深度测序，使大规模的基因组范围内的突变体筛选在不同的生长条件下必不可少的基因。我们分析了六个大规模的研究进行的单倍体菌株的三种酵母菌（酿酒酵母，裂殖酵母粟酒裂殖酵母，白色念珠菌），每一个诱变与两个三种不同的异源转座子（AcDs，爱马仕，和PiggyBac）。使用机器学习方法，我们评估了数据预测基因重要性的能力。重要的数据特征包括独立插入事件的足够数量和分布。由于头奖事件，所有转座子在插入位点偏好上都表现出一定的偏差，并且偏好特定的插入序列和短距离与长距离插入。对于PiggyBac，严格的靶序列限制了在具有很少或没有靶序列的基因中预测必要性的能力。机器学习方法还通过利用跨物种直向同源物来稳健地预测研究较少的物种中的基因功能。最后，比较了等基因二倍体和单倍体S。酿酒酵母分离物鉴定了几个单倍不足的基因，而大多数必需基因如预期的是隐性的。我们提供了转座子的选择和基因的重要性在真核单倍体微生物，如酵母，包括物种，已不太适合经典的遗传学研究的全基因组研究的推断的建议。本文的在线版本（10.1007/s 00294 -020-01096-6）包含补充材料，可供授权用户使用。
In vivo transposon mutagenesis, coupled with deep sequencing, enables large-scale genome-wide mutant screens for genes essential in different growth conditions. We analyzed six large-scale studies performed on haploid strains of three yeast species (Saccharomyces cerevisiae, Schizosaccaromyces pombe, and Candida albicans), each mutagenized with two of three different heterologous transposons (AcDs, Hermes, and PiggyBac). Using a machine-learning approach, we evaluated the ability of the data to predict gene essentiality. Important data features included sufficient numbers and distribution of independent insertion events. All transposons showed some bias in insertion site preference because of jackpot events, and preferences for specific insertion sequences and short-distance vs long-distance insertions. For PiggyBac, a stringent target sequence limited the ability to predict essentiality in genes with few or no target sequences. The machine learning approach also robustly predicted gene function in less well-studied species by leveraging cross-species orthologs. Finally, comparisons of isogenic diploid versus haploid S. cerevisiae isolates identified several genes that are haplo-insufficient, while most essential genes, as expected, were recessive. We provide recommendations for the choice of transposons and the inference of gene essentiality in genome-wide studies of eukaryotic haploid microbes such as yeasts, including species that have been less amenable to classical genetic studies. The online version of this article (10.1007/s00294-020-01096-6) contains supplementary material, which is available to authorized users.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
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作者：
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Biopython：用于计算分子生物学和生物信息学的免费 Python 工具。
DOI：
10.1093/bioinformatics/btp163
发表时间：
2009-06-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Cock PJ;Antao T;Chang JT;Chapman BA;Cox CJ;Dalke A;Friedberg I;Hamelryck T;Kauff F;Wilczynski B;de Hoon MJ
通讯作者：
de Hoon MJ
影响因子：
3.3
作者：
Lazarow, Katina;Du, My-Linh;Kunze, Reinhard
通讯作者：
Kunze, Reinhard
DOI：
10.1016/j.tig.2017.07.006
发表时间：
2017-11
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Kawakami K;Largaespada DA;Ivics Z
通讯作者：
Ivics Z