Kacsoh Balint Z, Greene Casey S, Bosco Giovanni
Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755.
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
G3 (Bethesda). 2017 Nov 6;7(11):3705-3718. doi: 10.1534/g3.117.300172.
High-throughput experiments are becoming increasingly common, and scientists must balance hypothesis-driven experiments with genome-wide data acquisition. We sought to predict novel genes involved in learning and long-term memory from existing public high-throughput data. We performed an analysis using PILGRM, which analyzes public gene expression compendia using machine learning. We evaluated the top prediction alongside genes involved in learning and memory in IMP, an interface for functional relationship networks. We identified (), a transcriptional repressor, histone deacetylase, as our top candidate. We find, through multiple, distinct assays, that has an active role as a modulator of memory retention in the fly and its function is required in the adult mushroom body. Depletion of specifically in neurons of the adult mushroom body, after cell division and neuronal development is complete, suggests that function is important for memory retention through regulation of neuronal activity, and not by altering neurodevelopment. Our study provides a previously uncharacterized role for as a possible regulator of neuronal plasticity at the interface of memory retention and memory extinction.
高通量实验正变得越来越普遍,科学家们必须在假设驱动的实验与全基因组数据采集之间取得平衡。我们试图从现有的公共高通量数据中预测参与学习和长期记忆的新基因。我们使用PILGRM进行了一项分析,该方法利用机器学习分析公共基因表达汇编。我们在IMP(一个功能关系网络界面)中评估了顶级预测结果以及参与学习和记忆的基因。我们确定转录抑制因子、组蛋白脱乙酰酶()为我们的顶级候选基因。我们通过多种不同的实验发现,()在果蝇记忆保留的调节中具有积极作用,并且其功能在成年蘑菇体中是必需的。在细胞分裂和神经元发育完成后,特异性地耗尽成年蘑菇体神经元中的(),表明()的功能对于通过调节神经元活动而非改变神经发育来保留记忆很重要。我们的研究为()在记忆保留和记忆消退界面作为神经元可塑性的可能调节因子提供了一个以前未被描述的作用。