Objective Clustering of Proteins Based on Subcellular Location Patterns

The goal of proteomics is the complete characterization of all proteins. Efforts to characterize subcellular location have been limited to assigning proteins to general categories of organelles. We have previously designed numerical features to describe location patterns in microscope images and developed automated classifiers that distinguish major subcellular patterns with high accuracy (including patterns not distinguishable by visual examination). The results suggest the feasibility of automatically determining which proteins share a single location pattern in a given cell type. We describe an automated method that selects the best feature set to describe images for a given collection of proteins and constructs an effective partitioning of the proteins by location. An example for a limited protein set is presented. As additional data become available, this approach can produce for the first time an objective systematics for protein location and provide an important starting point for discovering sequence motifs that determine localization.

[1]  J. Jarvik,et al.  CD-tagging: a new approach to gene and protein discovery and analysis. , 1996, BioTechniques.

[2]  Naoyuki Ichimura,et al.  Robust clustering based on a maximum‐likelihood method for estimating a suitable number of clusters , 1997 .

[3]  Palmer Encyclopedia of biostatistics , 1999, BMJ.

[4]  Stephen S. Taylor,et al.  A Visual Screen of a Gfp-Fusion Library Identifies a New Type of Nuclear Envelope Membrane Protein , 1999, The Journal of cell biology.

[5]  G. Church,et al.  Microarray analysis of the transcriptional network controlled by the photoreceptor homeobox gene Crx , 2000, Current Biology.

[6]  Robert F. Murphy,et al.  Towards a Systematics for Protein Subcellular Location: Quantitative Description of Protein Localization Patterns and Automated Analysis of Fluorescence Microscope Images , 2000, ISMB.

[7]  Joseph L. Thorley,et al.  RadCon: phylogenetic tree comparison and consensus , 2000, Bioinform..

[8]  George M. Church,et al.  Regulatory Networks Revealed by Transcriptional Profiling of Damaged Saccharomyces cerevisiae Cells: Rpn4 Links Base Excision Repair with Proteasomes , 2000, Molecular and Cellular Biology.

[9]  Robert F. Murphy,et al.  A neural network classifier capable of recognizing the patterns of all major subcellular structures in fluorescence microscope images of HeLa cells , 2001, Bioinform..

[10]  John C Reed,et al.  Advances in molecular labeling, high throughput imaging and machine intelligence portend powerful functional cellular biochemistry tools , 2002, Journal of cellular biochemistry. Supplement.

[11]  L Hennen,et al.  In vivo functional proteomics: mammalian genome annotation using CD-tagging. , 2002, BioTechniques.

[12]  A. Nakano Spinning-disk confocal microscopy -- a cutting-edge tool for imaging of membrane traffic. , 2002, Cell structure and function.

[13]  Robert F. Murphy,et al.  Robust classification of subcellular location patterns in fluorescence microscope images , 2002, Proceedings of the 12th IEEE Workshop on Neural Networks for Signal Processing.

[14]  Robert F. Murphy,et al.  Automated determination of protein subcellular locations from 3D fluorescence microscope images , 2002, Proceedings IEEE International Symposium on Biomedical Imaging.

[15]  Robert F. Murphy,et al.  Location proteomics: building subcellular location trees from high-resolution 3D fluorescence microscope images of randomly tagged proteins , 2003, SPIE BiOS.

[16]  D. Pe’er,et al.  Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data , 2003, Nature Genetics.

[17]  Kai Huang,et al.  Automated classification of subcellular patterns in multicell images without segmentation into single cells , 2004, 2004 2nd IEEE International Symposium on Biomedical Imaging: Nano to Macro (IEEE Cat No. 04EX821).

[18]  Kai Huang,et al.  Boosting accuracy of automated classification of fluorescence microscope images for location proteomics , 2004, BMC Bioinformatics.

[19]  R. Murphy,et al.  Robust classification of subcellular location patterns in high resolution 3D fluorescence microscope images , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[20]  Robert F Murphy,et al.  Automated interpretation of subcellular patterns from immunofluorescence microscopy. , 2004, Journal of immunological methods.