Department of Computer Science, Tufts University, 155 College Ave, Medford, MA 02155, USA.
BMC Bioinformatics. 2014 Feb 7;15:45. doi: 10.1186/1471-2105-15-45.
Recent increases in genomic studies of the developing human fetus and neonate have led to a need for widespread characterization of the functional roles of genes at different developmental stages. The Gene Ontology (GO), a valuable and widely-used resource for characterizing gene function, offers perhaps the most suitable functional annotation system for this purpose. However, due in part to the difficulty of studying molecular genetic effects in humans, even the current collection of comprehensive GO annotations for human genes and gene products often lacks adequate developmental context for scientists wishing to study gene function in the human fetus.
The Developmental FunctionaL Annotation at Tufts (DFLAT) project aims to improve the quality of analyses of fetal gene expression and regulation by curating human fetal gene functions using both manual and semi-automated GO procedures. Eligible annotations are then contributed to the GO database and included in GO releases of human data. DFLAT has produced a considerable body of functional annotation that we demonstrate provides valuable information about developmental genomics. A collection of gene sets (genes implicated in the same function or biological process), made by combining existing GO annotations with the 13,344 new DFLAT annotations, is available for use in novel analyses. Gene set analyses of expression in several data sets, including amniotic fluid RNA from fetuses with trisomies 21 and 18, umbilical cord blood, and blood from newborns with bronchopulmonary dysplasia, were conducted both with and without the DFLAT annotation.
Functional analysis of expression data using the DFLAT annotation increases the number of implicated gene sets, reflecting the DFLAT's improved representation of current knowledge. Blinded literature review supports the validity of newly significant findings obtained with the DFLAT annotations. Newly implicated significant gene sets also suggest specific hypotheses for future research. Overall, the DFLAT project contributes new functional annotation and gene sets likely to enhance our ability to interpret genomic studies of human fetal and neonatal development.
最近，对人类胎儿和新生儿发育基因组的研究不断增加，这使得人们需要广泛描述不同发育阶段基因的功能角色。基因本体论（GO）是一个用于描述基因功能的有价值且广泛使用的资源，它为这一目的提供了最合适的功能注释系统。然而，部分由于在人类中研究分子遗传效应的难度，即使是当前全面的人类基因和基因产物 GO 注释集合，对于希望研究人类胎儿基因功能的科学家来说，也往往缺乏足够的发育背景。
塔夫茨发育功能注释（DFLAT）项目旨在通过使用手动和半自动 GO 程序来改进人类胎儿基因表达和调控的分析质量，从而对人类胎儿基因功能进行注释。合格的注释将被提交到 GO 数据库中，并包含在 GO 发布的人类数据中。DFLAT 已经产生了大量的功能注释，我们证明这些注释提供了有关发育基因组学的有价值的信息。通过将现有的 GO 注释与 13344 个新的 DFLAT 注释相结合，生成了一组基因集（涉及同一功能或生物过程的基因），这些基因集可用于新的分析。对几个数据集的表达进行了基因集分析，包括唐氏综合征 21 号和 18 号三体胎儿羊水 RNA、脐带血和患有支气管肺发育不良的新生儿血液，分析时既使用了 DFLAT 注释，也没有使用 DFLAT 注释。
使用 DFLAT 注释对表达数据进行功能分析增加了被涉及的基因集数量，反映了 DFLAT 对当前知识的改进表示。盲法文献回顾支持了使用 DFLAT 注释获得的新的显著发现的有效性。新涉及的显著基因集也为未来的研究提供了具体的假设。总的来说，DFLAT 项目提供了新的功能注释和基因集，这可能会增强我们解释人类胎儿和新生儿发育的基因组研究的能力。
