title: Integrative subcellular proteomic analysis allows accurate prediction of human disease-causing genes.
abstract: Proteomic profiling on subcellular fractions provides invaluable information regarding both protein abundance and subcellular localization. When integrated with other data sets, it can greatly enhance our ability to predict gene function genome-wide. In this study, we performed a comprehensive proteomic analysis on the light-sensing compartment of photoreceptors called the outer segment (OS). By comparing with the protein profile obtained from the retina tissue depleted of OS, an enrichment score for each protein is calculated to quantify protein subcellular localization, and 84% accuracy is achieved compared with experimental data. By integrating the protein OS enrichment score, the protein abundance, and the retina transcriptome, the probability of a gene playing an essential function in photoreceptor cells is derived with high specificity and sensitivity. As a result, a list of genes that will likely result in human retinal disease when mutated was identified and validated by previous literature and/or animal model studies. Therefore, this new methodology demonstrates the synergy of combining subcellular fractionation proteomics with other omics data sets and is generally applicable to other tissues and diseases.
authors.affiliation: Structural and Computational Biology and Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, Texas 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Amol Onkar
authors.initials: AO
authors.lastname: Bajaj
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Aiden
authors.initials: A
authors.lastname: Eblimit
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Mingchu
authors.initials: M
authors.lastname: Xu
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Zachry T
authors.initials: ZT
authors.lastname: Soens
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Zhongqi
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Structural and Computational Biology and Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Theodore G
authors.initials: TG
authors.lastname: Wensel
authors.affiliation: Structural and Computational Biology and Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.affiliation: Structural and Computational Biology and Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, Texas 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
mesh_terms: D000818:Animals; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D010786:Photoreceptor Cells; D040901:Proteomics; D012164:Retinal Diseases / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D005136:Eye Proteins