A5082247454- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Neurobiology and Insect Physiology Research
- Molecular Biology Techniques and Applications
- Olfactory and Sensory Function Studies
- Glycosylation and Glycoproteins Research
- Genetics, Bioinformatics, and Biomedical Research
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
- Single-cell and spatial transcriptomics
- Lung Cancer Treatments and Mutations
- Plant biochemistry and biosynthesis
- Advanced Biosensing Techniques and Applications
- Ferroptosis and cancer prognosis
- Insect Pheromone Research and Control
- Medical Imaging and Pathology Studies
- Insect Pest Control Strategies
- Insect and Arachnid Ecology and Behavior
- Chemokine receptors and signaling
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Advanced biosensing and bioanalysis techniques
- Biosimilars and Bioanalytical Methods
Personalis (United States)
2017-2025
University of California, Riverside
2013-2016
Institut thématique Génétique, génomique et bioinformatique
2016
Abstract Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, applications are constrained by the sensitivity of clinically validated ctDNA approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically for ultrasensitive at 1–3 ppm with 99.9% specificity. Through an analysis 171 patients lung cancer from TRACERx study, we detected pre-operatively within 81% adenocarcinoma (LUAD), including 53% those...
1010 Background: Circulating tumor DNA (ctDNA) based detection of Molecular Residual Disease (MRD) in breast cancer patients presents a strategy to identify at high risk relapse, although current assays have limited sensitivity for low level ctDNA detection. In this study we profile early with an ultra-sensitive, whole genome sequencing-based, tumor-informed platform, and correlate the findings clinical outcomes. Methods: We analysed 598 plasma samples (median 8 samples/patient, range 2-14)...
Coding of information in the peripheral olfactory system depends on two fundamental factors: interaction individual odors with subsets odorant receptor repertoire and mode signaling that an receptor-odor elicits, activation or inhibition. We develop a cheminformatics pipeline predicts receptor–odorant interactions from large collection chemical structures (>240,000) for receptors have been tested to smaller panel odorants (∼100). Using computational approach, we first identify shared...
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,...
Abstract While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA and have not been examined. Here we investigate KRAS (ctKRAS) associations overall progression-free (OS/PFS) first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) patients receiving chemoimmunotherapy (“PRINCE”, NCT03214250), an independent cohort standard care (SOC) chemotherapy. For PRINCE, higher baseline plasma...
275 Background: While detection of MRD using ctDNA is prognostic for recurrence in CRC, some patients still recur prior to detection. VICTORI prospectively investigating NeXT Personal, an ultra-sensitive NGS-based assay, profile with resected CRC. Methods: Patients CRC treated curative intent (all stages) are tested a bespoke assay up ~1,800 tumor-informed single nucleotide variants (SNVs) identified from whole-genome sequencing. Plasma collected surgery, every 2 weeks post-surgery week 8...
Abstract Circulating tumor DNA (ctDNA) is a non-invasive biomarker increasingly used to detect residual or recurrent disease and monitor patient response therapy. However, there need for more sensitive tests that can achieve earlier detection of disease. The NeXT Personal® Dx (NPDx) ctDNA MRD test uses paired normal whole genome sequencing (WGS) design bespoke panel up ∼1800 variants relies on advanced noise suppression ultrasensitive down ∼1 part per million (PPM) (1x10-6 fraction) with...
Abstract Background: Circulating tumor (ctDNA) for detection of minimal residual disease (MRD) in colorectal cancers is prognostic, however, many are not detected prior to clinical recurrence. Chemotherapy and surgery may limit ctDNA due increased shedding DNA. We exploring the use an ultra-sensitive MRD assay (NeXT Personal®) a prospective study (VICTORI) undergoing resection, with aim determine optimal timepoint post-surgery detect MRD. Methods: Patients enrolled undergo whole genome...
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,...
270 Background: While immune checkpoint blockade (ICB) is used to treat metastatic deficient mismatch repair (dMMR) colorectal cancers (CRCs), such tumors are heterogeneous and resistance ICB frequent. To date, biomarkers that can consistently predict patient response lacking. We determined whether integrate tumor immune-related molecular mechanisms could response. Methods: Consecutive patients with dMMR CRCs (N=32) who had been treated anti-PD-1 therapy were profiled using a validated...
1009 Background: Patients with Stage II/III breast cancer that overexpresses the human epidermal growth factor-2 (HER2+) or is triple-negative (TNBC) generally receive upfront neoadjuvant therapy (NAT) before definitive surgery. Pathologic complete response (pCR) after NAT associated improved survival but a small proportion of patients remain at risk for recurrence. Circulating tumor DNA (ctDNA) in whose primary tumors have detectable mutations could improve identification who NAT. Methods:...
2561 Background: The potential of immune checkpoint inhibition (ICI) therapy is constrained by the inability to predict patient response. Circulating tumor DNA (ctDNA) has emerged as a promising tool for real-time response tracking and early prediction therapeutic outcomes. However, clinical utility ctDNA-based liquid biopsy faces critical challenge: reliable detection in low-shedding tumors during dramatic responses when ctDNA levels approach analytical threshold. We overcome this technical...
552 Background: NAC +/- immune checkpoint inhibitors is the standard of care for most early-stage TNBC patients. After and breast surgery, adjuvant treatment decisions rely on pathological complete response (pCR) status, which does not inform presence distant micrometastases. Blood-based assays ctDNA enable non-invasive monitoring residual disease levels at sensitivities down to 1 part-per-million (PPM). We report prognostic value ultrasensitive detection during in patients with TNBC....
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...
SUMMARY Despite shortcomings, N,N-Diethyl-3-methylbenzamide (DEET) has remained the gold-standard of insect repellents for >60 years. There are significant impediments to finding improved substitutes because molecular targets causing repellency unclear, new chemistries will require human-safety testing, and predicted costs development exorbitant. Here we identify shared structural features important using a supervised chemical-informatics method screen insilico >400,000 compounds...
588 Background: Neoadjuvant THP may become a new standard for pts with early stage HER2+ BC pending results of large ongoing trials. Although ctDNA persistence in the (neo)adjuvant setting is associated elevated risk distant recurrence, prevalence and dynamics are unknown. Methods: On single-arm phase II DAPHNe trial, II-III received 12 weeks neoadjuvant THP, followed by surgery adjuvant systemic therapy (tx) per physicians’ discretion (with no further chemotherapy case pCR). Plasma samples...
4025 Background: Metastatic esophagogastric cancer (mEGC) poses a significant challenge due to its poor long-term survival. The KeyLargo trial (NCT03342937) was single-arm phase II study of pembrolizumab combined with oxaliplatin and capecitabine in first line HER2 negative mEGC patients (pts). Although the revealed encouraging response rates, not all pts responded, underscoring need for improved biomarkers. To address this challenge, we utilized an ultra-sensitive tumor-informed circulating...
Odorants activate receptors in the peripheral olfactory neurons, which sends information to higher brain centers where behavioral valence is determined. Movement and airflow continuously change what odor plumes an animal encounters little known about effect one plume has on detection of another. Using simple Drosophila melanogaster larval model study this relationship we identify unexpected phenomenon: response attractant can be selectively blocked by previous exposure some odorants that...
9562 Background: Detection of molecular residual disease (MRD) via circulating tumor DNA (ctDNA) can identify therapeutic response/resistance months in advance imaging, and monitoring clinically actionable variant dynamics ctDNA may be important for guiding treatment. Despite this, adoption has been slow due to the reduced sensitivity reproducibility current approaches. Here, we profile melanoma patients receiving ICI over several years using an ultra-sensitive, tumor-informed platform,...
Abstract Detection of circulating tumor DNA (ctDNA) has been shown to correlate with clinical outcome oncology patients. Molecular residual disease (MRD) profiling by ctDNA is being rapidly deployed. Current tumor-informed MRD tests assess a relatively small number personalized variants, placing limits on their detection sensitivity and ultimately leading false-negative results due insufficient assay limit (LOD). Here we report performance evaluation the Personalis NeXT Personal assay, using...
e15625 Background: Detection of molecular residual disease (MRD) with ctDNA is highly prognostic for recurrence in CRC. However, many cancers still recur without detectable and increased lead time before clinical may create a window opportunity to intervene. Here we apply an ultra-sensitive assay, NeXT Personal, profile patients the VICTORI study, prospective cohort CRC managed curative-intent treatment. Methods: To date, first 33 have undergone panel creation. Personal was employed...
2510 Background: Determining which patients will achieve clinical benefit from immune checkpoint inhibition (ICI) therapy remains an open question. Liquid biopsy tests to assess baseline and early dynamics of circulating tumor DNA (ctDNA) may allow clinicians track response more granularly predict ICI or resistance prior imaging. However, lack sensitivity hinder accurate detection low ctDNA levels in tumors with shedding rates during substantial drops clearance response. Methods: This study...