A5011486405- Cancer Genomics and Diagnostics
- Prostate Cancer Treatment and Research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- Pulsed Power Technology Applications
- Genetic factors in colorectal cancer
- Acute Myeloid Leukemia Research
- Molecular Biology Techniques and Applications
- Yersinia bacterium, plague, ectoparasites research
- Genomics and Chromatin Dynamics
- Hedgehog Signaling Pathway Studies
- Bladder and Urothelial Cancer Treatments
- Genomics and Rare Diseases
- Gyrotron and Vacuum Electronics Research
- Electrostatic Discharge in Electronics
- RNA Research and Splicing
- Bacillus and Francisella bacterial research
- Single-cell and spatial transcriptomics
- Geophysics and Sensor Technology
- Acoustic Wave Resonator Technologies
- SARS-CoV-2 and COVID-19 Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Electromagnetic Effects on Materials
- Labour Market and Migration
New York Genome Center
2022-2025
Radiance Technologies (United States)
2023
Cornell University
2023
Emmes (United States)
2018-2022
Advanced urothelial cancer is a frequently lethal disease characterized by marked genetic heterogeneity
The U2AF1 gene is a core part of mRNA splicing machinery and frequently contains somatic mutations that contribute to oncogenesis in myelodysplastic syndrome, acute myeloid leukemia, other cancers. A change introduced the GRCh38 version human reference build prevents detection this gene, others, by variant calling pipelines. This study describes problem detail shows modified with unchanged coordinates can be used ameliorate issue. encodes component mutated syndrome (MDS) cancers.1Graubert...
Here, we present Lancet2, an open-source somatic variant caller designed to improve detection of small variants in short-read sequencing data. Lancet2 introduces significant enhancements, including: 1) Improved discovery and genotyping through partial order multiple sequence alignment assembled haplotype contigs re-alignment sample reads the best supporting allele. 2) Optimized scoring with Explainable Machine Learning models leading better filtering throughout sensitivity scale. 3)...
Aggressive variant and androgen receptor (AR)-independent castration resistant prostate cancers (CRPC) represent the most significant diagnostic therapeutic challenges in cancer. This study examined a case of simultaneous progression both adenocarcinoma squamous tumors from same common origin. Using whole-genome transcriptome sequencing 17 samples collected over >6 years, we established clonal relationship all samples, defined shared complex structural variants, demonstrated divergent...
Background: Patient-derived cancer models advance therapeutic development and are essential to studies of treatment resistance mechanisms. The Human Cancer Models Initiative (HCMI) has created 665 patient-derived models, including organoids, neurospheres, conditionally reprogrammed cells, all paired with patient tumors clinical annotations. This resource provides an opportunity study genomic conservation divergence during model at scale in a large pan-cancer cohort matched tumor-model pairs....
Abstract Advancing precision oncology requires a diverse and robust repository of patient-derived cancer models that faithfully reflect the clinical, therapeutic, molecular attributes patients’ tumor. Traditional models, while invaluable, often lack sufficient clinical data fail to capture genetic phenotypic complexity human cancers, limiting their translational relevance. To address these challenges, Human Cancer Models Initiative (HCMI) generated 665 next-generation from over 2,500 donors...
Abstract Background: Up to 40% of patients with muscle-invasive bladder cancer (MIBC) are ineligible receive standard-of-care neoadjuvant cisplatin-based chemotherapy, creating a significant unmet need for effective therapies. Based on our prior findings the high prevalence somatic cell cycle alterations in MIBC, we conducted first window-of-opportunity investigator-initiated trial CDK4/6 inhibitor abemaciclib (abema) followed by radical cystectomy (RC) MIBC (CLONEVO, NCT03837821). Methods:...
Genomic rearrangements are a hallmark of most childhood tumors, including medulloblastoma, one the common brain tumors in children, but their causes remain largely unknown. Here, we show that PiggyBac transposable element derived 5 (Pgbd5) promotes tumor development multiple developmentally accurate mouse models Sonic Hedgehog (SHH) medulloblastoma. Most Pgbd5-deficient mice do not develop while maintaining normal cerebellar development. Ectopic activation SHH signaling is sufficient to...
Background: Tularemia is a potential biological weapon due to its high infectivity and ease of dissemination. This study aimed characterize the innate adaptive responses induced by two different lots live attenuated tularemia vaccine compare them other well-characterized viral immune responses. Methods: Microarray analyses were performed on human peripheral blood mononuclear cells (PBMCs) determine changes in transcriptional activity that correlated with detected cellular phenotyping,...
The immune response to live-attenuated Francisella tularensis vaccine and its host evasion mechanisms are incompletely understood. Using RNA-Seq LC–MS on samples collected pre-vaccination at days 1, 2, 7, 14 post-vaccination, we identified differentially expressed genes in PBMCs, metabolites serum, enriched pathways, that correlated with T cell B responses, or gene expression modules. While an early activation of interferon α/β signaling was observed, several innate pathways including TLR,...
Intracranial metastases in prostate cancer are uncommon but clinically aggressive. A detailed molecular characterization of intracranial would improve our understanding their pathogenesis and the search for new treatment strategies. We evaluated clinical characteristics 36 patients with metastatic to either dura or brain parenchyma. performed whole genome sequencing (WGS) 10 metastases, as well WGS primary tumors from men who later developed disease (n = 6) nonbrain 36). This first study led...
, the cause of plague, could be weaponized. Unfortunately, development new vaccines is limited by lack correlates protection. We used pre- and post-vaccination sera peripheral blood mononuclear cells from a flagellin adjuvanted F1/V vaccine trial to evaluate for protective markers. Here, we report first time in humans that inverse caspase-3 levels, which are measures antibody, significantly increased 29% 75% on days 14 28 post-second vaccination, respectively. In addition, there were...
ABSTRACT Circulating cell-free DNA (ccfDNA) sequencing for low-burden cancer monitoring is limited by sparsity of circulating tumor (ctDNA), the abundance genomic material within a plasma sample, and pre-analytical error rates due to library preparation, errors. Sequencing costs have historically favored development deep targeted approaches overcoming in ctDNA detection, but these techniques are ccfDNA samples, which imposes ceiling on maximal depth coverage panels. Whole genome (WGS) an...
With increasing interest in ab initio protein design, there is a desire to be able fully explore the design space of insertions and deletions. Nature inserts deletes residues optimize energy function, but allowing variable length indels context an interactive session presents challenges with regard speed accuracy.Here we present new module (INDEL) for InteractiveRosetta which allows user specify range lengths desired indel, returns set low backbones matter seconds. To make loop search fast,...
Abstract The U2AF1 gene is a core part of mRNA splicing machinery and frequently contains somatic mutations that contribute to oncogenesis in MDS, AML, other cancers. A change introduced the GRCh38 version human reference build prevents this from being detected by many variant calling pipelines. We describe problem detail show modified with unchanged coordinates can be used ameliorate issue. This available at https://zenodo.org/record/4684553 (doi:10.5281/zenodo.4684553)
Abstract Advanced urothelial cancer is a frequently lethal disease characterized by marked genetic heterogeneity. In this study, we investigate the evolution of genomic signatures caused endogenous and external mutagenic stimuli their interplay with complex structural variants. We superimposed mutational phylogenetic analyses matched serial tumors from patients to define evolutionary patterns these processes. show that APOBEC3-induced mutations are clonal early, whereas bursts comprising...
Abstract Genomic rearrangements are a hallmark of most solid tumors, including medulloblastoma, one the common brain tumors in children. Childhood cancers involve dysregulated cell development, but their mutational causes remain largely unknown. One forms medulloblastoma is caused by ectopic activation Sonic Hedgehog (SHH) signaling cerebellar granule progenitors, associated with genetic deletions, amplifications, and other oncogenic chromosomal rearrangements. Here, we show that PiggyBac...
Ribosomal profiling is an emerging experimental technology to measure protein synthesis by sequencing short mRNA fragments undergoing translation in ribosomes. Applied on the genome wide scale, this a powerful tool profile global within cell populations of interest. Such information can be utilized for biomarker discovery and detection treatment-responsive genes. However, analysis ribosomal data requires careful preprocessing reduce impact artifacts dedicated statistical methods visualizing...
Abstract In many areas of oncology, we lack sensitive tumor-burden monitoring to guide critical decision making. While circulating tumor DNA (ctDNA) promises enable disease monitoring, this approach is limited by the sparsity ctDNA in plasma. To overcome challenge, error-corrected deep targeted sequencing has been proposed. Nonetheless, framework low number genomic equivalents (GEs, ~103/mL plasma), imposing a ceiling on effective depth. We have previously shown that genome-wide mutational...
Spiral generators can be used to generate high-voltage pulses on the order of singles hundreds nanoseconds with a single switch. They act as energy storage, voltage multiplication, and sometimes an RF source all in one compact package. This design makes them attractive for high pulse generation volume weight sensitive applications. Previous work has primarily leveraged spark gap devices initiation switch operation. Some limited explored using thyristors replacement gaps. paper explores use...
Spiral generators can be used to generate high-voltage pulses on the order of singles hundreds nanoseconds with a single switch. They act as energy storage, voltage multiplication, and sometimes an RF source all in one compact package. This design makes them attractive for high pulse generation volume weight sensitive applications. One challenge designing characterizing spiral is ability calculate both input output impedance device. paper presents method measuring generator using frequency...
Ferroelectric materials are a subset of Piezoelectric which have remnant polarization under no external electric field. Previous work performed by Radiance Technologies as well others within the pulsed power community demonstrated that energy stored in ferroelectrics can be extracted through explosive shock to generate high voltages. One major limitations these devices is output voltage and limited leakage currents, premature material cracking, physical size bulk ferroelectric ceramics. In...