Genoppi is an open-source software for robust and standardized integration of proteomic and genetic data

Nat Commun. 2021 May 10;12(1):2580. doi: 10.1038/s41467-021-22648-5.

Abstract

Combining genetic and cell-type-specific proteomic datasets can generate biological insights and therapeutic hypotheses, but a technical and statistical framework for such analyses is lacking. Here, we present an open-source computational tool called Genoppi (lagelab.org/genoppi) that enables robust, standardized, and intuitive integration of quantitative proteomic results with genetic data. We use Genoppi to analyze 16 cell-type-specific protein interaction datasets of four proteins (BCL2, TDP-43, MDM2, PTEN) involved in cancer and neurological disease. Through systematic quality control of the data and integration with published protein interactions, we show a general pattern of both cell-type-independent and cell-type-specific interactions across three cancer cell types and one human iPSC-derived neuronal cell type. Furthermore, through the integration of proteomic and genetic datasets in Genoppi, our results suggest that the neuron-specific interactions of these proteins are mediating their genetic involvement in neurodegenerative diseases. Importantly, our analyses suggest that human iPSC-derived neurons are a relevant model system for studying the involvement of BCL2 and TDP-43 in amyotrophic lateral sclerosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cells, Cultured
  • Computational Biology / methods*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Genome-Wide Association Study / methods*
  • Genomics
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Mutation
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Neurons / metabolism*
  • Polymorphism, Single Nucleotide
  • Protein Binding
  • Proteomics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Software*
  • Tandem Mass Spectrometry

Substances

  • BCL2 protein, human
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • TARDBP protein, human
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2