title: Deep convolutional neural networks for annotating gene expression patterns in the mouse brain.
abstract: BACKGROUND
  Profiling gene expression in brain structures at various spatial and temporal scales is essential to understanding how genes regulate the development of brain structures. The Allen Developing Mouse Brain Atlas provides high-resolution 3-D in situ hybridization (ISH) gene expression patterns in multiple developing stages of the mouse brain. Currently, the ISH images are annotated with anatomical terms manually. In this paper, we propose a computational approach to annotate gene expression pattern images in the mouse brain at various structural levels over the course of development.
  
  
  RESULTS
  We applied deep convolutional neural network that was trained on a large set of natural images to extract features from the ISH images of developing mouse brain. As a baseline representation, we applied invariant image feature descriptors to capture local statistics from ISH images and used the bag-of-words approach to build image-level representations. Both types of features from multiple ISH image sections of the entire brain were then combined to build 3-D, brain-wide gene expression representations. We employed regularized learning methods for discriminating gene expression patterns in different brain structures. Results show that our approach of using convolutional model as feature extractors achieved superior performance in annotating gene expression patterns at multiple levels of brain structures throughout four developing ages. Overall, we achieved average AUC of 0.894 ± 0.014, as compared with 0.820 ± 0.046 yielded by the bag-of-words approach.
  
  
  CONCLUSIONS
  Deep convolutional neural network model trained on natural image sets and applied to gene expression pattern annotation tasks yielded superior performance, demonstrating its transfer learning property is applicable to such biological image sets.
authors.affiliation: Department of Computer Science, Old Dominion University, Norfolk, 23529, VA, USA. tzeng@cs.odu.edu.
authors.forename: Tao
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Department of Computer Science, Old Dominion University, Norfolk, 23529, VA, USA. rli@cs.odu.edu.
authors.forename: Rongjian
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Computer Science, Old Dominion University, Norfolk, 23529, VA, USA. mukka@cs.odu.edu.
authors.forename: Ravi
authors.initials: R
authors.lastname: Mukkamala
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, 48109, MI, USA. jpye@umich.edu.|Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, 48109, MI, USA. jpye@umich.edu.
authors.forename: Jieping
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Computer Science, Old Dominion University, Norfolk, 23529, VA, USA. sji@cs.odu.edu.
authors.forename: Shuiwang
authors.initials: S
authors.lastname: Ji
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D051379:Mice; D058977:Molecular Sequence Annotation; D016571:Neural Networks, Computer; D010363:Pattern Recognition, Automated