From fuzziness to precision medicine: on the rapidly evolving proteomics with implications in mitochondrial connectivity to rare human disease

Khaled A Aly; Mohamed Taha Moutaoufik; Sadhna Phanse; Qingzhou Zhang; Mohan Babu

doi:10.1016/j.isci.2020.102030

From fuzziness to precision medicine: on the rapidly evolving proteomics with implications in mitochondrial connectivity to rare human disease

iScience. 2021 Jan 6;24(2):102030. doi: 10.1016/j.isci.2020.102030. eCollection 2021 Feb 19.

Authors

Khaled A Aly¹, Mohamed Taha Moutaoufik¹, Sadhna Phanse¹, Qingzhou Zhang¹, Mohan Babu¹

Affiliation

¹ Department of Biochemistry, University of Regina, Regina, SK, Canada.

Abstract

Mitochondrial (mt) dysfunction is linked to rare diseases (RDs) such as respiratory chain complex (RCC) deficiency, MELAS, and ARSACS. Yet, how altered mt protein networks contribute to these ailments remains understudied. In this perspective article, we identified 21 mt proteins from public repositories that associate with RCC deficiency, MELAS, or ARSACS, engaging in a relatively small number of protein-protein interactions (PPIs), underscoring the need for advanced proteomic and interactomic platforms to uncover the complete scope of mt connectivity to RDs. Accordingly, we discuss innovative untargeted label-free proteomics in identifying RD-specific mt or other macromolecular assemblies and mapping of protein networks in complex tissue, organoid, and stem cell-differentiated neurons. Furthermore, tag- and label-based proteomics, genealogical proteomics, and combinatorial affinity purification-mass spectrometry, along with advancements in detecting and integrating transient PPIs with single-cell proteomics and transcriptomics, collectively offer seminal follow-ups to enrich for RD-relevant networks, with implications in RD precision medicine.

Keywords: Complex Systems; Disease; Proteomics; Systems Biology.

Publication types

Review

Grants and funding

R01 GM106019/GM/NIGMS NIH HHS/United States