arXiv subjects

Gue Su Chang

Publications and source records attributed to Gue Su Chang.

3 recordsLinked to original sources

arXiv2025

ImmunoNX: a robust bioinformatics workflow to support personalized neoantigen vaccine trials

Personalized neoantigen vaccines represent a promising immunotherapy approach that harnesses tumor-specific antigens to stimulate anti-tumor immune responses. However, the design of these vaccines requires sophisticated computational workflows to predict and prioritize neoantigen candidates from patient sequencing data, coupled with rigorous review to ensure candidate quality. While numerous computational tools exist for neoantigen prediction, to our knowledge, there are no established protocols detailing the complete process from raw sequencing data through systematic candidate selection. Here, we present ImmunoNX (Immunogenomics Neoantigen eXplorer), an end-to-end protocol for neoantigen prediction and vaccine design that has supported over 185 patients across 11 clinical trials. The workflow integrates tumor DNA/RNA and matched normal DNA sequencing data through a computational pipeline built with Workflow Definition Language (WDL) and executed via Cromwell on Google Cloud Platform. ImmunoNX employs consensus-based variant calling, in-silico HLA typing, and pVACtools for neoantigen prediction. Additionally, we describe a two-stage immunogenomics review process with prioritization of neoantigen candidates, enabled by pVACview, followed by manual assessment of variants using the Integrative Genomics Viewer (IGV). This workflow enables vaccine design in under three months. We demonstrate the protocol using the HCC1395 breast cancer cell line dataset, identifying 78 high-confidence neoantigen candidates from 322 initial predictions. Although demonstrated here for vaccine development, this workflow can be adapted for diverse neoantigen therapies and experiments. Therefore, this protocol provides the research community with a reproducible, version-controlled framework for designing personalized neoantigen vaccines, supported by detailed documentation, example datasets, and open-source code.

q-bio.GN↗

arXiv2010

Theories on PHYlogenetic ReconstructioN (PHYRN)

The inability to resolve deep node relationships of highly divergent/rapidly evolving protein families is a major factor that stymies evolutionary studies. In this manuscript, we propose a Multiple Sequence Alignment (MSA) independent method to infer evolutionary relationships. We previously demonstrated that phylogenetic profiles built using position specific scoring matrices (PSSMs) are capable of constructing informative evolutionary histories(1;2). In this manuscript, we theorize that PSSMs derived specifically from the query sequences used to construct the phylogenetic tree will improve this method for the study of rapidly evolving proteins. To test this theory, we performed phylogenetic analyses of a benchmark protein superfamily (reverse transcriptases (RT)) as well as simulated datasets. When we compare the results obtained from our method, PHYlogenetic ReconstructioN (PHYRN), with other MSA dependent methods, we observe that PHYRN provides a 4- to 100-fold increase in accurate measurements at deep nodes. As phylogenetic profiles are used as the information source, rather than MSA, we propose PHYRN as a paradigm shift in studying evolution when MSA approaches fail. Perhaps most importantly, due to the improvements in our computational approach and the availability of vast amount of sequencing data, PHYRN is scalable to thousands of sequences. Taken together with PHYRNs adaptability to any protein family, this method can serve as a tool for resolving ambiguities in evolutionary studies of rapidly evolving/highly divergent protein families.

q-bio.PE↗

arXiv2008

Phylogenetic Profiles as a Unified Framework for Measuring Protein Structure, Function and Evolution

The sequence of amino acids in a protein is believed to determine its native state structure, which in turn is related to the functionality of the protein. In addition, information pertaining to evolutionary relationships is contained in homologous sequences. One powerful method for inferring these sequence attributes is through comparison of a query sequence with reference sequences that contain significant homology and whose structure, function, and/or evolutionary relationships are already known. In spite of decades of concerted work, there is no simple framework for deducing structure, function, and evolutionary (SF&E) relationships directly from sequence information alone, especially when the pair-wise identity is less than a threshold figure ~25% [1,2]. However, recent research has shown that sequence identity as low as 8% is sufficient to yield common structure/function relationships and sequence identities as large as 88% may yet result in distinct structure and function [3,4]. Starting with a basic premise that protein sequence encodes information about SF&E, one might ask how one could tease out these measures in an unbiased manner. Here we present a unified framework for inferring SF&E from sequence information using a knowledge-based approach which generates phylogenetic profiles in an unbiased manner. We illustrate the power of phylogenetic profiles generated using the Gestalt Domain Detection Algorithm Basic Local Alignment Tool (GDDA-BLAST) to derive structural domains, functional annotation, and evolutionary relationships for a host of ion-channels and human proteins of unknown function. These data are in excellent accord with published data and new experiments. Our results suggest that there is a wealth of previously unexplored information in protein sequence.

q-bio.QM↗