Vermeirssen Vanessa, De Clercq Inge, Van Parys Thomas, Van Breusegem Frank, Van de Peer Yves
Department of Plant Systems Biology, VIB, 9052 Gent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Gent, Belgium
Department of Plant Systems Biology, VIB, 9052 Gent, Belgium Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Gent, Belgium.
Plant Cell. 2014 Dec;26(12):4656-79. doi: 10.1105/tpc.114.131417. Epub 2014 Dec 30.
The abiotic stress response in plants is complex and tightly controlled by gene regulation. We present an abiotic stress gene regulatory network of 200,014 interactions for 11,938 target genes by integrating four complementary reverse-engineering solutions through average rank aggregation on an Arabidopsis thaliana microarray expression compendium. This ensemble performed the most robustly in benchmarking and greatly expands upon the availability of interactions currently reported. Besides recovering 1182 known regulatory interactions, cis-regulatory motifs and coherent functionalities of target genes corresponded with the predicted transcription factors. We provide a valuable resource of 572 abiotic stress modules of coregulated genes with functional and regulatory information, from which we deduced functional relationships for 1966 uncharacterized genes and many regulators. Using gain- and loss-of-function mutants of seven transcription factors grown under control and salt stress conditions, we experimentally validated 141 out of 271 predictions (52% precision) for 102 selected genes and mapped 148 additional transcription factor-gene regulatory interactions (49% recall). We identified an intricate core oxidative stress regulatory network where NAC13, NAC053, ERF6, WRKY6, and NAC032 transcription factors interconnect and function in detoxification. Our work shows that ensemble reverse-engineering can generate robust biological hypotheses of gene regulation in a multicellular eukaryote that can be tested by medium-throughput experimental validation.
植物中的非生物胁迫反应是复杂的，并且受到基因调控的严格控制。我们通过对拟南芥微阵列表达纲要进行平均秩聚合，整合四种互补的逆向工程解决方案，构建了一个包含11,938个靶基因、200,014个相互作用的非生物胁迫基因调控网络。该整合方法在基准测试中表现最为稳健，极大地扩展了目前已报道的相互作用的数量。除了恢复1182个已知的调控相互作用外，靶基因的顺式调控基序和连贯功能与预测的转录因子相对应。我们提供了一个有价值的资源，包含572个具有功能和调控信息的共调控基因的非生物胁迫模块，从中我们推断出1966个未表征基因和许多调控因子的功能关系。利用在对照和盐胁迫条件下生长的7个转录因子的功能获得和功能缺失突变体，我们通过实验验证了102个选定基因的271个预测中的141个（精度为52%），并绘制了另外148个转录因子-基因调控相互作用（召回率为49%）。我们鉴定出一个复杂的核心氧化应激调控网络，其中NAC13、NAC053、ERF6、WRKY6和NAC032转录因子相互连接并在解毒过程中发挥作用。我们的工作表明，整合逆向工程可以在多细胞真核生物中生成关于基因调控的可靠生物学假设，并可以通过中等通量的实验验证进行检验。
