BrainProt™: unraveling insights into meningioma tumorigenesis and neurological signaling cascades

The burgeoning interest in understanding the complexities of the human brain and its associated diseases has spurred the creation of diverse consortia, databases, and repositories. Innovations in Omics technologies have been instrumental in understanding underlying mechanisms, resulting in an abundance of brain-related data dispersed across multiple platforms. Our initiative aimed to develop an integrated platform, BrainProt™ (https://www.brainprot.org/), facilitating user-friendly and swift exploration of brain functions and diseases. This platform encompasses six interconnected domains, such as the Inter-Hemispheric Brain Proteome Map and Brain Phospho Map, and includes extensive data on disease markers, drug interactions, clinical trials, and multi-omics information for over 50 human brain diseases. By using BrainProt™, we understood Meningioma tumorigenesis, highlighting the platform's potential to reveal novel insights into brain tumors.

Meningioma, constituting a significant proportion of brain tumors, has posed challenges to healthcare due to its rising incidence in recent years. Current diagnostic and treatment approaches largely rely on MRI and surgical interventions, highlighting the need for early diagnostic markers and tailored therapeutic strategies. Our study utilized BrainProt™'s Brain Disease Marker Curator (BDMC) section, coupled with our own quantitative clinical proteomics experiments, to identify and validate grade-specific markers for Meningioma in a cohort of Indian patients. Integrating Multiple Reaction Monitoring (MRM) validation and Machine Learning (ML) techniques, we successfully delineated segregation patterns between low-grade and high-grade Meningiomas. Furthermore, through meta-omics analysis, we identified altered signaling pathways and therapeutic targets, particularly highlighting Integrin Linked Kinase (ILK) as a key regulator in Meningioma tumorigenesis. Experimental inhibition of ILK demonstrated anti-proliferative effects and potential for therapeutic intervention. These findings highlight the significance of BrainProt™ in identifying disease markers and elucidating signaling cascades, showcasing its value in clinical research and neurobiology.

References:

Biswas, D. et al. Srivastava S. (2021). Deciphering the interregional and interhemisphere proteome of the human brain in the context of the human proteome project. JPR, 20(12), 5280-5293.Biswas, D. et al. Srivastava S. (2022). Deep Phosphoproteome Landscape of Interhemispheric Functionality of Neuroanatomical Regions of the Human Brain. JPR, 22(4), 1043-1055.Biswas, D. et al. Srivastava S. (2023). BrainProt(TM) 3.0: Understanding Human Brain Diseases using comprehensively curated & Integrated OMICS datasets. bioRxiv, 2023.06.21.545851Biswas, D. et al. Srivastava S. (2023). Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma. Cells, 12(20), 2483.