Please join Yu Lab graduate student Shagun Gupta as she defends her PhD thesis in Computational Biology!

Date: Thursday November 14, 2024;

Time: 4:00pm;

Location: G01 Biotech.

Graduate Field of Computational Biology 

MEMO 

To: Members of the Graduate Field of Computational Biology 

FROM: Philipp Messer, Director of Graduate Studies DATE: November 4, 2024 

Shagun Gupta has scheduled her B exam on Thursday, November 14, 2024, at 4:00 p.m., in G01 Biotechnology and on the Webinar link here. Shagun’s title is “Mass Spectrometry Based Proteomics and Its Applications in Understanding Disease Progression and Designing Therapeutic Strategies.” Her dissertation advisor is Haiyuan Yu, Professor, Computational Biology. 

Abstract: 

Quantitative proteomics offers transformative insights into molecular mechanisms underlying complex diseases; however, the inherent noise and variability in proteomic data pose significant challenges for accurate signal detection. This led to the development of the Maximal Aggregation of Good protein signal from Mass spectrometric data (MAGMa) tool, which leverages rigorous statistical testing to achieve a balance between sensitivity and specificity, effectively filtering out noise and enabling robust identification of subtle, true biological signals. MAGMa’s utility was validated on benchmarking datasets, where it consistently outperformed existing methods in identifying accurate interaction signals. 

MAGMa was applied to disease models with high therapeutic relevance, including SARS-CoV-2 and onco-fusion-driven cancers. In SARS-CoV-2 studies, MAGMa revealed a detailed host-pathogen interactome by identifying novel viral-host protein interactions. This approach led to the discovery of potential antiviral targets, with the drug carvedilol demonstrating promising antiviral effects in follow-up studies. In cancer models, MAGMa enabled us to dissect the altered protein interaction networks driven by oncogenic fusion proteins, identifying critical perturbations in the SWI/SNF chromatin remodeling complex in sarcoma. These findings shed light on the molecular underpinnings of fusion-mediated oncogenesis and open avenues for targeted cancer therapies. 

This corpus of work explores how network dynamics inform disease progression and the potential for computational tools to refine protein biomarkers as close phenotypic readouts. Results presented herein demonstrate how rigorous statistical methods can enhance the precision of proteomic analyses, making it possible to unravel complex biological interactions and prioritize drug targets. MAGMa provides researchers with a powerful tool to deepen insights into disease mechanisms and accelerate therapeutic discovery across a range of pathologies. 

Publications 

•Gupta S.*, et al. MAGMa: Your Comprehensive Tool for Differential Expression Analysis inMass-Spectrometry Proteomic Data. In review; 2024.

•Gupta S.*, et al. Deciphering the Molecular Mechanisms of Gene Fusion-DrivenRewiring of Protein Interaction Networks in Cancer. In preparation; 2024

•Zhou Y.*, Liu Y.*, Gupta S.*, Paramo M., Hou Y., et al. A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology andpotential host therapeutic targets. Nature Biotechnology 41, 128–139 (2023).

•Kumar Y.*, Gupta S.*, et al. Inferring protein-protein interaction networks from massspectrometry-based proteomic approaches: a mini-review. Computational and StructuralBiotechnology Journal 17 (2019): 805-811.

•Wierbowski S.D*., … Gupta S., … Yu H. A 3D structural SARS-CoV-2–humaninteractome to explore genetic and drug perturbations. Nature Methods 18, 1477–1488(2021).

•Lanz, M. C.*, Yugandhar, K.*, Gupta S., Sanford, E. J., Fa¸ca, V. M., Vega, S., …Smolka, M. B. (2021). In-depth and 3-dimensional exploration of the budding yeastphosphoproteome. EMBO reports, 22(2), e51121.

•Faca, V. M.*, Sanford, E. J.*, Tieu, J., Comstock, W., Gupta S., Marshall, S., … Smolka, M.B.(2020). Maximized quantitative phosphoproteomics allows high confidence dissection ofthe DNA damage signaling network. Scientific reports, 10(1), 1-15.

•Zhang Y*., … Gupta S., … Yu H. A multiscale functional map of somatic mutations incancer integrating protein structure and network topology. Nature Communications,(2024).

*: equal contribution 

Join Webinar

https://cornell.zoom.us/j/94506128561?pwd=OI4XMi1wK9ZA1PAFNin1fAmbwAFKJz.1

Please contact us at compbio@cornell.edu with any questions. Thank you!

Department of Computational Biology | Cornell University, 102 Weill Hall, Ithaca, NY 14853 | Office 607.255.5488 | https://cals.cornell.edu/computational-biology | College of Agriculture and Life Sciences