Computational Analysis of Drug Response in Biological Networks

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Augustin  Luna
Organization: NATIONAL LIBRARY OF MEDICINE
Fiscal Year: 2024
Award: $882,387
Funding agency: National Library of Medicine

1. Computational Analysis of Sarcoma Pharmacogenomics
Sarcomas are a diverse group of rare malignancies composed of multiple different clinical and molecular subtypes. Due to their rarity and heterogeneity, basic, translational, and clinical research in sarcoma has trailed behind that of other cancers. With colleagues, Luna lab group members worked to conduct analyses in the following areas related to sarcomas: 

* The biological relevance of sarcoma cell lines as preclinical models based on oncogenic fusions
* The mutation and mutational burden characteristics of sarcoma cell lines
* Predictive biomarkers of drug response using sarcoma cell line pharmacogenomics data

2. Machine Learning Analysis of Single-Cell Perturbation Datasets
Perturbation experiments probe the response of cells or cellular systems to changes in conditions (e.g., drug treatment). Large-scale single-cell perturbation–response screens enable exploration of complex cellular behavior inaccessible in bulk measurements. Reliable analysis of increasingly large perturbation datasets requires efficient statistical tools to harness large numbers of cells and perturbations. There is presently little convention for statistical comparison of response profiles in perturbation studies. Luna lab group members worked to conduct analyses worked to develop a method for quantification of perturbation effects and significance testing as well as a measure between sets of single-cell expression profiles.

3. Graph-Based Computational Analysis for Drug-Target Identification in COVID-19
The COVID-19 global pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 Disease Map project was a large-scale community effort uniting 277 scientists from 130 Institutions that worked to better understand SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. Luna lab group members worked as part of this effort to develop C19DMap-Neo4j graph database of SARS-CoV-2-host interactions, as well as understand to analyze this dataset in relation to Clinical Trials (clinicaltrials.gov) data for drug repurposing opportunities. 

4. Continued Development of the Systems Biology Graphical Notation (SBGN) for Exchange of Cellular Signaling Knowledge 
Systems Biology Graphical Notation project, an effort to standardize the graphical notation used in maps of biological networks and processes from gene regulation, to metabolism, to cellular signaling. The effort enables scientists to visually represent networks of biochemical interactions in a standard, unambiguous way. The SBGN effort is a community effort that draws on ideas from numerous researchers to develop a widely usable representation formalism. Luna lab group members continued to develop SBGN based on community feedback concentrated on remaining areas ambiguities that can arise in some SBGN diagrams; an example of this involves duplication of visual elements and the semantics of these duplications. Additionally, Luna lab group members continued to work on tools to simplify the use of SBGN by the wider research community; these efforts focus on simplifying the generation of SBGN diagrams.

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