A5086660741- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Genomics and Phylogenetic Studies
- Chromosomal and Genetic Variations
- Single-cell and spatial transcriptomics
- Genomics and Rare Diseases
- Ferroptosis and cancer prognosis
- Lymphoma Diagnosis and Treatment
- Molecular Biology Techniques and Applications
- Forensic and Genetic Research
- Insect symbiosis and bacterial influences
- RNA and protein synthesis mechanisms
- Plant and animal studies
- Evolution and Genetic Dynamics
- Glycosylation and Glycoproteins Research
- Colorectal Cancer Treatments and Studies
- Plant Molecular Biology Research
- Plant Reproductive Biology
Personalis (United States)
2019-2023
Indiana University Bloomington
2014-2020
Abstract Background New sequencing technologies have lowered financial barriers to whole genome sequencing, but resulting assemblies are often fragmented and far from ‘finished’. Updating multi-scaffold drafts chromosome-level status can be achieved through experimental mapping or re-sequencing efforts. Avoiding the costs associated with such approaches, comparative genomic analysis of gene order conservation (synteny) predict scaffold neighbours (adjacencies) offers a potentially useful...
Genomes sequenced using short-read, next-generation sequencing technologies can have many errors and may be fragmented into thousands of small contigs. These incomplete assemblies lead to in gene identification, such that single genes spread across multiple contigs are annotated as separate models. Such biases confound inferences about the number identity within species, well gain loss between species. We present AGOUTI (Annotated Genome Optimization Using Transcriptome Information), a tool...
Abstract Purpose: While immune checkpoint blockade (ICB) has become a pillar of cancer treatment, biomarkers that consistently predict patient response remain elusive due to the complex mechanisms driving tumors. We hypothesized multi-dimensional approach modeling both tumor and immune-related molecular would better ICB than simpler mutation-focused biomarkers, such as mutational burden (TMB). Experimental Design: Tumors from cohort patients with late-stage melanoma (n = 51) were profiled...
Major histocompatibility complex (MHC)-bound peptides that originate from tumor-specific genetic alterations, known as neoantigens, are an important class of anticancer therapeutic targets. Accurately predicting peptide presentation by MHC complexes is a key aspect discovering therapeutically relevant neoantigens. Technological improvements in mass-spectrometry-based immunopeptidomics and advanced modeling techniques have vastly improved prediction over the past two decades. However,...
Current de novo whole-genome sequencing approaches often are inadequate for organisms lacking substantial preexisting genetic data. Problems with these methods manifest as: large numbers of scaffolds that not ordered within chromosomes or assigned to individual chromosomes, misassembly allelic sequences as separate loci when the individual(s) being sequenced heterozygous, and collapse recently duplicated into a single locus, regardless levels heterozygosity. Here we propose new approach...
Major histocompatibility complex (MHC)–bound peptides that originate from tumor-specific genetic alterations, known as neoantigens, are an important class of anticancer therapeutic targets. Accurately predicting peptide presentation by MHC complexes is a key aspect discovering therapeutically relevant neoantigens. Technological improvements in mass spectrometry–based immunopeptidomics and advanced modeling techniques have vastly improved prediction over the past 2 decades. However,...
Abstract Human leukocyte antigen loss of heterozygosity (HLA LOH) allows cancer cells to escape immune recognition by deleting HLA alleles, causing the suppressed presentation tumor neoantigens. Despite its importance in immunotherapy response, few methods exist detect LOH, and their accuracy is not well understood. Here, we develop DASH (Deletion Allele-Specific HLAs), a machine learning-based algorithm LOH from paired tumor-normal sequencing data. With cell line mixtures, demonstrate...
Abstract A goal of speciation genetics is to understand how the genetic components underlying interspecific reproductive barriers originate within species. Unilateral incompatibility (UI) a postmating prezygotic barrier in which pollen rejection female tract (style) occurs only one direction an cross. Natural variation strength UI has been observed among populations species wild tomato clade. In some cases, molecular loci self-incompatibility (SI) are associated with this UI, but mechanistic...
Abstract Summary Current genome assemblies consist of thousands contigs. These incomplete and fragmented lead to errors in gene identification, such that single genes spread across multiple contigs are annotated as separate models. We present AGOUTI (Annotated Genome Optimization Using Transcriptome Information), a tool uses RNA-seq data simultaneously combine into scaffolds models show improves both the contiguity accuracy annotation, providing updated versions each output. Availability The...
Recent genetic studies and whole-genome sequencing projects have greatly improved our understanding of human variation clinically actionable information. Smaller ethnic populations, however, remain underrepresented in both individual large-scale efforts hence present an opportunity to discover new variants biomedical demographic significance. This report describes the analysis a genome obtained from Serbian origin, introducing tens thousands previously unknown currently available pool....
Abstract Background New sequencing technologies have lowered financial barriers to whole genome sequencing, but resulting assemblies are often fragmented and far from ‘finished’. Updating multi-scaffold drafts chromosome-level status can be achieved through experimental mapping or re-sequencing efforts. Avoiding the costs associated with such approaches, comparative genomic analysis of gene order conservation (synteny) predict scaffold neighbours (adjacencies) offers a potentially useful...
Abstract An increasing number of studies have demonstrated the potential use circulating cell-free DNA (cfDNA) for diagnosis, prognosis, and disease progression monitoring. However, many these utilize assays covering a limited set genes, typically tens to few hundred therefore can miss biologically clinically important genetic alterations such as repair pathways, immuno-modulatory mechanisms resistance changes in neoantigen status. To address this, we developed whole-exome scale cfDNA...
e18030 Background: Human leukocyte antigen loss of heterozygosity (HLA LOH) restricts immune recognition tumors by limiting the major histocompatibility complex (MHC) presentation neoantigens to T cells and correlates with reduced response checkpoint blockade therapy (ICB) in non-small cell lung cancer. To explore mechanism behind impairment HLA LOH on ICB, we analyzed relationship between pathway, neoantigen ICB a head neck squamous carcinoma (HNSCC) cohort. Methods: Following baseline...
6557 Background: The reduced scope, and number of genes profiled by typical liquid biopsy panels can result in missed biomarkers including neoantigens, which may change with treatment, as well potentially undetected resistance mechanisms pathways beyond the scope targets typically captured panels. To address these limitations, we used a whole-exome scale monitoring platform, NeXT Liquid Biopsy, to analyze head neck squamous cell carcinoma (HNSCC) patients that have received anti-PD1 therapy....
Abstract Major histocompatibility complex (MHC)-bound peptides that originate from tumor-specific genetic alterations, known as neoantigens, are an important class of anti-cancer therapeutic targets. Accurately predicting peptide presentation by MHC complexes is a key aspect discovering therapeutically relevant neoantigens. Technological improvements in mass-spectrometry-based immunopeptidomics and advanced modeling techniques have vastly improved prediction over the past two decades....
Abstract Human leukocyte antigen loss of heterozygosity (HLA LOH) allows cancer cells to escape immune recognition by deleting HLA alleles, causing the suppressed presentation tumor neoantigens that would otherwise bind them. Despite its importance in immunotherapy response, few methods exist detect LOH, and their accuracy is not well understood. Here, we develop DASH ( D eletion A llele- S pecific H LAs), a novel machine learning-based algorithm LOH from paired tumor-normal sequencing data....
Abstract Background Typical liquid biopsy panels capture a relatively small number of variants, and likely under-represent the heterogeneity resistance in late-stage cancers. This reduced scope can result overlooked therapeutic biomarkers which respond dynamically to treatment, as well potentially missed mechanisms pathway-level events. To address challenges associated with identifying multiple concurrent heterogeneous individual patients, we evaluated longitudinal whole exome sequencing...
Supplementary Data from Prediction of Immunotherapy Response in Melanoma through Combined Modeling Neoantigen Burden and Immune-Related Resistance Mechanisms
Supplementary Figure from Prediction of Immunotherapy Response in Melanoma through Combined Modeling Neoantigen Burden and Immune-Related Resistance Mechanisms