Dataset Information

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

ABSTRACT: This submission contains human protein interaction datasets of four proteins (BCL2, TDP-43, MDM2, PTEN) across three cancer cell lines (G401, T47D, A375) and one iPSC-derived neuronal cell line (glutamatergic patterned induced neuron, GPiN). The data were generated to demonstrate the utility of Genoppi (lagelab.org/genoppi), an open-source computational tool that enables integration of quantitative proteomic results with genetic data. Our analyses show a general pattern of both cell-type-independent and cell-type-specific interactions for the tested proteins. In particular, our results suggest that the neuron-specific interactions of BCL2 and TDP-43 are mediating their genetic involvement in amyotrophic lateral sclerosis.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Kasper Lage

LAB HEAD: Kasper Lage

PROVIDER: PXD022667 | Pride | 2021-02-10

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	191107LGPSAM06218_RABMONO-T13.raw	Raw
	191107LGPSAM06218_RABMONO-T14.raw	Raw
	191107LGPSAM06218_RABMONO-T15.raw	Raw
	191107LGPSAM06218_RABMONO-T16.raw	Raw
	191107LGPSAM06218_RABMONO-T17.raw	Raw

Items per page:

1 - 5 of 66

Publications

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

Pintacuda Greta G Lassen Frederik H FH Hsu Yu-Han H YH Kim April A Martín Jacqueline M JM Malolepsza Edyta E Lim Justin K JK Fornelos Nadine N Eggan Kevin C KC Lage Kasper K

Nature communications 20210510 1

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- ...[more]

PMID: 33972534

Similar Datasets

Project description:Aims: Loss of nuclear TDP-43 characterises sporadic and most familial forms of amyotrophic lateral sclerosis (ALS). TDP-43 (encoded by TARDBP) has multiple roles in RNA processing. We aimed to determine whether 1) RNA splicing dysregulation is present in lower motor neurons in ALS and in a motor neuron-like cell model, and 2) TARDBP mutations (mtTARDBP) are associated with aberrant RNA splicing using patient-derived fibroblasts. Methods: Affymetrix exon arrays were used to study mRNA expression and splicing in lower motor neurons obtained by laser capture microdissection of autopsy tissue from individuals with sporadic ALS and TDP-43 proteinopathy. Findings were confirmed by qRT-PCR and in NSC34 motor neuronal cells following shRNA-mediated TDP-43 depletion. Exon arrays and immunohistochemistry were used to study mRNA splicing and TDP-43 expression in fibroblasts from patients with mtTARDBP-associated, sporadic and mutant SOD1-associated ALS. Results: We found altered expression of spliceosome components in motor neurons and widespread aberrations of mRNA splicing that specifically affected genes involved in ribonucleotide binding. This was confirmed in TDP-43 depleted NSC34 cells. Fibroblasts with mtTARDBP showed loss of nuclear TDP-43 protein and demonstrated similar changes in splicing and gene expression, that were not present in fibroblasts from patients with sporadic or SOD1-related ALS. Conclusion: Loss of nuclear TDP-43 is associated with RNA processing abnormalities in ALS motor neurons, patient-derived cells with mtTARDBP, and following artificial TDP-43 depletion, suggesting that splicing dysregulation directly contributes to disease pathogenesis. Key functional pathways affected include those central to RNA metabolism. RNA was extracted from fibroblasts grown from neurologically healthy controls (n=6) and 3 groups of patients with ALS: 1) sporadic cases (n=6); 2) cases due to mutations of SOD1 (n=4); 3) cases due to mutations of TARDBP (n=3). The three ALS groups were compared to the controls.