A5070571906- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Genomic variations and chromosomal abnormalities
- RNA modifications and cancer
- Sarcoma Diagnosis and Treatment
- Veterinary Oncology Research
- Peptidase Inhibition and Analysis
- Cardiac tumors and thrombi
- Vascular Tumors and Angiosarcomas
- Angiogenesis and VEGF in Cancer
- Prenatal Screening and Diagnostics
- Viral gastroenteritis research and epidemiology
- Zoonotic diseases and public health
- Genomics and Rare Diseases
- Bacillus and Francisella bacterial research
- Glioma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Hydrological Forecasting Using AI
- Neurogenetic and Muscular Disorders Research
- RNA Interference and Gene Delivery
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Social Work Education and Practice
- Amyloidosis: Diagnosis, Treatment, Outcomes
Mayo Clinic
2021-2025
Brigham and Women's Hospital
2025
Harvard University
2025
Mayo Clinic in Arizona
2022-2023
Mayo Clinic in Florida
2023
WinnMed
2023
Cornell University
2016-2022
Département Santé Animale
2022
ORCID
2021
Saint Louis University
2017
Our genomes encode a wealth of transcription initiation regions (TIRs) that can be identified by their distinctive patterns actively elongating RNA polymerase. We previously introduced dREG to identify TIRs using PRO-seq data. Here, we introduce an efficient new implementation uses data both uni- and bidirectionally transcribed with 70% improvement in accuracy, three- fourfold higher resolution, >100-fold increases computational efficiency. Using novel strategy based on statistical...
Background: Autosomal recessive juvenile Parkinson disease (ARJP) is an early-onset neurodegenerative disorder characterized by Parkinsonian motor symptoms with slow progression and preserved cognition. Biallelic pathogenic variants within the PRKN gene are associated ARJP. Among variants, deletions a frequent occurrence may be identified through chromosomal microarray testing. Methods: Here we present case two intragenic initially as secondary finding using microarray. One deletion was...
How DNA sequence affects the dynamics and position of RNA Polymerase II (Pol II) during transcription remains poorly understood. Here, we used naturally occurring genetic variation in F1 hybrid mice to explore how differences affect genome-wide distribution Pol II. We measured orientation eight organs collected from heterozygous using ChRO-seq. Our data revealed a strong basis for precise coordinates initiation promoter proximal pause, allowing us redefine molecular models core...
Abstract The advent of animal husbandry and hunting increased human exposure to zoonotic pathogens. To understand how a disease may have influenced evolution, we study changes in expression anthrax toxin receptor 2 ( ANTXR2 ), which encodes cell surface protein necessary for Bacillus anthracis virulence toxins cause disease. In immune cells, is 8-fold down-regulated all available samples compared non-human primates, indicating regulatory early the evolution modern humans. We also observe...
Abstract Background Canine visceral hemangiosarcoma (HSA) is a highly aggressive cancer of endothelial origin that closely resembles angiosarcoma in humans, both clinically and histopathologically. Currently there an unmet need for new diagnostics therapies forms this disease. The goal study was to utilize Chromatin run-on sequencing (ChRO-seq) immunohistochemistry (IHC) identify gene protein expression signatures may be important drivers HSA progression. Results ChRO-seq performed on tissue...
Rgtsvm provides a fast and flexible support vector machine (SVM) implementation for the R language. The distinguishing feature of is that classification regression tasks are implemented on graphical processing unit (GPU), allowing libraries to scale millions examples with >100-fold improvement in performance over existing implementations. Nevertheless, retains parity has an interface compatible popular e1071 SVM package R. Altogether, enables large models be created by both experienced...
Background β2-microglobulin amyloidosis was first described in the 1980s as a protein deposition disease associated with long-term haemodialysis. More recently, two inherited forms resulting from separate point mutations gene have been identified. In this report, we detail novel β2M variant, P32L, caused by unique dinucleotide mutation that is linked to systemic hereditary amyloidosis.Methods Three family members Portuguese kinship featured cardiomyopathy, requiring organ transplantation one...
Abstract Our genomes encode a wealth of transcription initiation regions (TIRs) that can be identified by their distinctive patterns actively elongating RNA polymerase. We previously introduced dREG to identify TIRs using PRO-seq data. Here we introduce an efficient new implementation uses data both uni- and bidirectionally transcribed with 70% improvements in accuracy, 3-4-fold higher resolution, >100-fold increases computational efficiency. Using novel strategy based on statistical...
Abstract The role of histone modifications in transcription remains incompletely understood. Here we used experimental perturbations combined with sensitive machine learning tools that infer the distribution marks using maps nascent transcription. Transcription predicted variation active and complex chromatin states, like bivalent promoters, down to single-nucleosome resolution at an accuracy rivaled correspondence between independent ChIP-seq experiments. Blocking rapidly removed two...
Abstract How DNA sequence affects the dynamics and position of RNA Polymerase II (Pol II) during transcription remains poorly understood. Here we used naturally occurring genetic variation in F1 hybrid mice to explore how differences affect genome-wide distribution Pol II. We measured orientation eight organs collected from heterozygous using ChRO-seq. Our data revealed a strong basis for precise coordinates initiation promoter proximal pause, allowing us redefine molecular models core...
Abstract Transcriptional regulatory changes have been shown to contribute phenotypic differences between species, but many questions remain about how gene expression evolves. Here we report the first comparative study of nascent transcription in primates. We used PRO-seq map actively transcribing RNA polymerases resting and activated CD4+ T-cells multiple human, chimpanzee, rhesus macaque individuals, with rodents as outgroups. This approach allowed us measure separately from...
The MN1::ETV6 gene fusion resulting from t(12;22)(p13;q12) has been rarely reported in myeloid neoplasms. We describe a 69-year-old male with newly diagnosed acute leukemia (AML) erythroid differentiation and demonstrated by conventional chromosome studies. Subsequent fluorescence situ hybridization studies balanced ETV6 rearrangement (at 12p13). To further characterize this translocation, whole-genome sequencing was performed which confirmed t(12;22) breakpoints involving the MN1 genes....
Abstract Background Despite clinically demonstrated accuracy in next generation sequencing (NGS) data, many clinical laboratories continue to confirm variants with Sanger sequencing, which increases cost of testing and turnaround time. Several studies have assessed the NGS detecting single nucleotide variants; however, less has been reported about insertion, deletion, deletion-insertion (indels). Methods We performed a retrospective analysis from 2015–2022 indel results subset targeted gene...
Abstract The role of histone modifications in transcription remains incompletely understood. Here we used experimental perturbations combined with sensitive machine learning tools that infer the distribution marks using maps nascent transcription. Transcription predicted variation active and complex chromatin states, like bivalent promoters, down to single-nucleosome resolution at an accuracy rivaled correspondence between independent ChIP-seq experiments. Blocking rapidly removed two...
Abstract The advent of animal husbandry and hunting increased human exposure to zoonotic pathogens. To understand how a disease influenced evolution, we studied changes in expression anthrax toxin receptor 2 ( ANTXR2 ), which encodes cell surface protein necessary for Bacillus anthracis virulence toxins cause disease. In immune cells, was 8-fold down-regulated all available samples compared non-human primates, indicating regulatory early the evolution modern humans. We also observed multiple...
Abstract Glioblastoma (GBM), IDH-wildtype (WT) is currently defined as an IDH-WT and H3-WT diffuse astrocytic glioma with molecular diagnostic features including whole +7/−10, TERT promoter (TERTp) mutation, EGFR amplification and/or morphological such necrosis microvascular proliferation. To further understand the diversity of copy number signatures GBM, IDHWT evaluate utility other recurrent changes, we analyzed paired chromosomal microarray next-generation sequencing mutational profiling...
Abstract Background Canine visceral hemangiosarcoma (HSA) is a highly aggressive cancer of endothelial origin that closely resembles human angiosarcoma, both clinically and histopathologically. Currently there an unmet need for new diagnostics therapies forms this disease. The goal study was to utilize ChRO-seq immunohistochemistry (IHC) identify gene protein expression signatures may be important drivers HSA progression. Methods Chromatin run-on sequencing (ChRO-seq) performed on tissue...