دورية أكاديمية
Genoppi is an open-source software for robust and standardized integration of proteomic and genetic data.
العنوان: | Genoppi is an open-source software for robust and standardized integration of proteomic and genetic data. |
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المؤلفون: | Pintacuda G; Stanley Center at Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA., Lassen FH; Stanley Center at Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Hsu YH; Stanley Center at Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA., Kim A; Stanley Center at Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.; Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA., Martín JM; Stanley Center at Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA., Malolepsza E; Stanley Center at Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA., Lim JK; Stanley Center at Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.; Massachusetts Institute of Technology, Cambridge, MA, USA., Fornelos N; Stanley Center at Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA., Eggan KC; Stanley Center at Broad Institute of MIT and Harvard, Cambridge, MA, USA. eggan@mcb.harvard.edu.; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA. eggan@mcb.harvard.edu., Lage K; Stanley Center at Broad Institute of MIT and Harvard, Cambridge, MA, USA. lage.kasper@mgh.harvard.edu.; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. lage.kasper@mgh.harvard.edu.; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark. lage.kasper@mgh.harvard.edu. |
المصدر: | Nature communications [Nat Commun] 2021 May 10; Vol. 12 (1), pp. 2580. Date of Electronic Publication: 2021 May 10. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Software*, Computational Biology/*methods , Genome-Wide Association Study/*methods , Induced Pluripotent Stem Cells/*metabolism , Neoplasms/*genetics , Neoplasms/*metabolism , Neurons/*metabolism, Cell Line, Tumor ; Cells, Cultured ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Genomics ; Humans ; Mutation ; 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 ; Tandem Mass Spectrometry |
مستخلص: | 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. |
References: | Nat Genet. 2019 Mar;51(3):431-444. (PMID: 30804558) Nucleic Acids Res. 1983 Mar 11;11(5):1475-89. (PMID: 6828386) Nature. 2020 May;581(7809):434-443. (PMID: 32461654) Nucleic Acids Res. 2015 Apr 20;43(7):e47. (PMID: 25605792) J Proteome Res. 2010 Feb 5;9(2):1104-20. (PMID: 20020773) Nucleic Acids Res. 2017 Jan 4;45(D1):D619-D625. (PMID: 27799471) Nucleic Acids Res. 2020 Jan 8;48(D1):D682-D688. (PMID: 31691826) Nature. 2015 Oct 1;526(7571):68-74. (PMID: 26432245) Nat Methods. 2017 Jan;14(1):61-64. (PMID: 27892958) Am J Hum Genet. 2007 Sep;81(3):559-75. (PMID: 17701901) EMBO Mol Med. 2018 Jan;10(1):48-62. (PMID: 29191947) Oncogene. 2008 Oct 27;27(50):6398-406. (PMID: 18955968) Neuron. 2004 Jul 8;43(1):19-30. (PMID: 15233914) Nature. 2013 Jul 11;499(7457):214-218. (PMID: 23770567) Science. 2015 Jan 23;347(6220):1260419. (PMID: 25613900) Cell. 2021 May 27;184(11):3022-3040.e28. (PMID: 33961781) Leukemia. 2018 Nov;32(11):2459-2470. (PMID: 29654271) Nat Methods. 2017 Jun 29;14(7):645-646. (PMID: 28661499) Nucleic Acids Res. 2018 Mar 16;46(5):2699. (PMID: 29425356) Ann Neurol. 1996 Sep;40(3):379-86. (PMID: 8797527) Biochim Biophys Acta. 2004 Mar 1;1644(2-3):189-203. (PMID: 14996503) Science. 2014 Jan 17;343(6168):301-5. (PMID: 24292625) J Proteomics. 2014 Apr 04;100:37-43. (PMID: 24513533) Nat Genet. 2000 May;25(1):25-9. (PMID: 10802651) Nat Genet. 2012 Dec;44(12):1355-9. (PMID: 23104006) Cell. 2015 Jul 16;162(2):425-440. (PMID: 26186194) Nature. 2014 Jul 24;511(7510):421-7. (PMID: 25056061) Nat Biotechnol. 2008 Dec;26(12):1367-72. (PMID: 19029910) Nat Methods. 2014 Aug;11(8):868-74. (PMID: 24952909) Am J Hum Genet. 2010 Jul 9;87(1):139-45. (PMID: 20598278) Nat Genet. 2018 Jul;50(7):937-943. (PMID: 29955178) Front Mol Neurosci. 2019 Feb 14;12:25. (PMID: 30837838) BMC Bioinformatics. 2008 Sep 30;9:405. (PMID: 18823568) PLoS Genet. 2011 Jan 13;7(1):e1001273. (PMID: 21249183) Cell Syst. 2015 Dec 23;1(6):417-425. (PMID: 26771021) Nat Commun. 2021 May 10;12(1):2580. (PMID: 33972534) Trends Cell Biol. 2014 Apr;24(4):257-64. (PMID: 24284280) Nucleic Acids Res. 2019 Jan 8;47(D1):D1005-D1012. (PMID: 30445434) Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517) Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450. (PMID: 30395289) Nat Biotechnol. 2007 Mar;25(3):309-16. (PMID: 17344885) Nat Commun. 2018 Jan 18;9(1):286. (PMID: 29348612) Nat Neurosci. 2019 Dec;22(12):1966-1974. (PMID: 31768050) Nucleic Acids Res. 2019 Jan 8;47(D1):D330-D338. (PMID: 30395331) Nat Methods. 2019 Jan;16(1):63-66. (PMID: 30573815) Stat Appl Genet Mol Biol. 2004;3:Article3. (PMID: 16646809) Nat Methods. 2016 Sep;13(9):731-40. (PMID: 27348712) Cell Rep. 2018 May 22;23(8):2509-2523. (PMID: 29791859) Med Genet. 2018;30(2):252-258. (PMID: 30220791) Biochim Biophys Acta. 2014 Oct;1842(10):1971-1980. (PMID: 24892209) Nat Genet. 2018 Apr;50(4):621-629. (PMID: 29632380) Cell. 2020 Oct 1;183(1):269-283.e19. (PMID: 32916130) Cell. 2020 Feb 6;180(3):568-584.e23. (PMID: 31981491) Cell Death Differ. 2018 Jan;25(1):37-45. (PMID: 29099482) Am J Hum Genet. 2012 Jul 13;91(1):152-62. (PMID: 22703881) |
معلومات مُعتمدة: | T32 DK110919 United States DK NIDDK NIH HHS; U01 DK078616 United States DK NIDDK NIH HHS; R01 MH109903 United States MH NIMH NIH HHS; T32 HG002295 United States HG NHGRI NIH HHS; U01 MH121499 United States MH NIMH NIH HHS |
المشرفين على المادة: | 0 (BCL2 protein, human) 0 (DNA-Binding Proteins) 0 (Proto-Oncogene Proteins c-bcl-2) 0 (TARDBP protein, human) EC 2.3.2.27 (MDM2 protein, human) EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) |
تواريخ الأحداث: | Date Created: 20210511 Date Completed: 20210602 Latest Revision: 20240402 |
رمز التحديث: | 20240402 |
مُعرف محوري في PubMed: | PMC8110583 |
DOI: | 10.1038/s41467-021-22648-5 |
PMID: | 33972534 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
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DOI: | 10.1038/s41467-021-22648-5 |