Rizzo Gaia, Veronese Mattia, Expert Paul, Turkheimer Federico E, Bertoldo Alessandra
Department of Information Engineering, University of Padova, Padova, Italy.
Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
PLoS One. 2016 Feb 16;11(2):e0148744. doi: 10.1371/journal.pone.0148744. eCollection 2016.
Brain-wide mRNA mappings offer a great potential for neuroscience research as they can provide information about system proteomics. In a previous work we have correlated mRNA maps with the binding patterns of radioligands targeting specific molecular systems and imaged with positron emission tomography (PET) in unrelated control groups. This approach is potentially applicable to any imaging modality as long as an efficient procedure of imaging-genomic matching is provided. In the original work we considered mRNA brain maps of the whole human genome derived from the Allen human brain database (ABA) and we performed the analysis with a specific region-based segmentation with a resolution that was limited by the PET data parcellation. There we identified the need for a platform for imaging-genomic integration that should be usable with any imaging modalities and fully exploit the high resolution mapping of ABA dataset.
In this work we present MENGA (Multimodal Environment for Neuroimaging and Genomic Analysis), a software platform that allows the investigation of the correlation patterns between neuroimaging data of any sort (both functional and structural) with mRNA gene expression profiles derived from the ABA database at high resolution.
We applied MENGA to six different imaging datasets from three modalities (PET, single photon emission tomography and magnetic resonance imaging) targeting the dopamine and serotonin receptor systems and the myelin molecular structure. We further investigated imaging-genomic correlations in the case of mismatch between selected proteins and imaging targets.
全脑mRNA图谱为神经科学研究提供了巨大潜力,因为它们可以提供有关系统蛋白质组学的信息。在之前的一项工作中,我们已将mRNA图谱与靶向特定分子系统的放射性配体的结合模式相关联,并在不相关的对照组中用正电子发射断层扫描(PET)进行成像。只要提供一种有效的成像 - 基因组匹配程序,这种方法就可能适用于任何成像方式。在最初的工作中,我们考虑了源自艾伦人类大脑数据库(ABA)的全人类基因组的mRNA脑图谱,并使用基于特定区域的分割方法进行分析,其分辨率受PET数据分割的限制。在那里,我们确定需要一个用于成像 - 基因组整合的平台,该平台应可用于任何成像方式,并充分利用ABA数据集的高分辨率图谱。
在这项工作中,我们展示了MENGA(用于神经成像和基因组分析的多模态环境),这是一个软件平台,它允许以高分辨率研究任何类型(功能和结构)的神经成像数据与源自ABA数据库的mRNA基因表达谱之间的相关模式。
我们将MENGA应用于来自三种成像方式(PET、单光子发射断层扫描和磁共振成像)的六个不同成像数据集,这些数据集针对多巴胺和5-羟色胺受体系统以及髓磷脂分子结构。我们进一步研究了所选蛋白质与成像靶点不匹配情况下的成像 - 基因组相关性。