A5047389561- Cancer Genomics and Diagnostics
- Genomics and Phylogenetic Studies
- Genomics and Rare Diseases
- Molecular Biology Techniques and Applications
- PARP inhibition in cancer therapy
- Epigenetics and DNA Methylation
- Genomic variations and chromosomal abnormalities
- Cancer therapeutics and mechanisms
- CRISPR and Genetic Engineering
- Evolution and Genetic Dynamics
- RNA modifications and cancer
- Artificial Intelligence in Healthcare and Education
- RNA and protein synthesis mechanisms
- Genetic factors in colorectal cancer
- Lung Cancer Diagnosis and Treatment
- Radiomics and Machine Learning in Medical Imaging
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Clusterin in disease pathology
- Cell Image Analysis Techniques
- DNA Repair Mechanisms
- Gut microbiota and health
- Cancer Mechanisms and Therapy
- Plant Disease Resistance and Genetics
- Advances in Oncology and Radiotherapy
- Genetics and Neurodevelopmental Disorders
University of California, San Diego
2020-2025
La Jolla Bioengineering Institute
2020-2025
Massachusetts General Hospital
2021-2023
Global Cancer Institute
2022
Abstract Gains and losses of DNA are prevalent in cancer emerge as a consequence inter-related processes replication stress, mitotic errors, spindle multipolarity breakage–fusion–bridge cycles, among others, which may lead to chromosomal instability aneuploidy 1,2 . These copy number alterations contribute initiation, progression therapeutic resistance 3–5 Here we present conceptual framework examine the patterns human that is widely applicable diverse data types, including whole-genome...
Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for
PURPOSE Cancers with homologous recombination deficiency (HRD) can benefit from platinum salts and poly(ADP-ribose) polymerase inhibitors. Standard diagnostic tests for detecting HRD require molecular profiling, which is not universally available. METHODS We trained DeepHRD, a deep learning platform predicting hematoxylin eosin (H&E)–stained histopathological slides, using primary breast (n = 1,008) ovarian 459) cancers The Cancer Genome Atlas (TCGA). DeepHRD was compared four standard...
SUMMARY Mutational signature analysis is commonly performed in genomic studies surveying cancer and normal somatic tissues. Here we present SigProfilerExtractor, an automated tool for accurate de novo extraction of mutational signatures all types mutations. Benchmarking with a total 34 distinct scenarios encompassing 2,500 simulated operative more than 60,000 unique synthetic genomes 20,000 exomes demonstrates that SigProfilerExtractor outperforms thirteen other tools across datasets without...
Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). Here, we further explore how tobacco exposure contributes to development by mutational signature analysis 265 whole-genome sequenced HNC from eight countries. Six tobacco-associated signatures were detected, including some not previously reported. Differences in incidence between countries corresponded differences mutation burdens signatures, consistent dominant role causation. found burden...
All cancers harbor somatic mutations in their genomes. In principle, affecting between one and fifty base pairs are generally classified as small mutational events. Conversely, large events affect more than pairs, and, most cases, they encompass copy-number structural variants many thousands of pairs. Prior studies have demonstrated that examining patterns can be leveraged to provide both biological clinical insights, thus, resulting an extensive repertoire tools for evaluating Recently,...
ABSTRACT Colorectal cancer incidence rates vary geographically and have changed over time. Notably, in the past two decades, of early-onset colorectal cancer, affecting individuals under age 50 years, has doubled many countries. The reasons for this increase are unknown. Here, we investigate whether mutational processes contribute to geographic age-related differences by examining 981 genomes from 11 No major were found microsatellite unstable cancers, but variations mutation burden...
(Abstracted from J Clin Oncol 2024;42:3550–3560) The field of precision medicine attempts to treat conditions with combinations that are tailored the individual and disease; oncology uses techniques identify molecular defects in tumors them targeted interventions. For both breast ovarian cancers, previous literature has shown homologous recombination deficiency (HRD) can be treated poly(ADP-ribose) polymerase (PARP) inhibitors platinum salts.
Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). We explore how tobacco exposure contributes to development by mutational signature analysis 265 whole-genome sequenced HNC samples from eight countries. Six tobacco-associated signatures were detected, including some not previously reported. Differences in incidence between countries corresponded differences mutation burdens signatures, consistent dominant role causation. found burden...
Abstract Acquired drug resistance to even the most effective anti-cancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired have been identified 1‒6 , underlying molecular mechanisms shaping tumor evolution during treatment are incompletely understood. The extent which therapy actively drives by promoting mutagenic processes 7 or simply provides selective pressure necessary for outgrowth drug-resistant clones 8 open question. Here, we report that lung...
ABSTRACT Breast and ovarian cancers harboring homologous recombination deficiencies (HRD) can benefit from platinum-based chemotherapies PARP inhibitors. Standard diagnostic tests for detecting HRD utilize molecular profiling, which is not universally available especially medically underserved populations. Here, we trained a deep learning approach predicting genomically derived scores routinely sampled hematoxylin eosin (H&E)-stained histopathological slides. For breast cancer, the was...
All cancers harbor somatic mutations in their genomes. In principle, affecting between one and fifty base pairs are generally classified as small mutational events. Conversely, large events affect more than pairs, and, most cases, they encompass copy-number structural variants many thousands of pairs. Prior studies have demonstrated that examining patterns can be leveraged to provide both biological clinical insights, thus, resulting an extensive repertoire tools for evaluating Recently,...
Breast and ovarian cancers harboring homologous recombination deficiency (HRD) are sensitive to PARP inhibitors platinum chemotherapy. Conventionally, detecting HRD involves screening for defects in BRCA1, BRCA2, other relevant genes. Recent analyses have shown that exhibit characteristic mutational patterns due the activities of HRD-associated signatures. At least three machine learning tools exist based on patterns. Here, using sequencing data from 1,043 breast 182 cancers, we trained...
ABSTRACT The gains and losses of DNA that emerge as a consequence mitotic errors chromosomal instability are prevalent in cancer. These copy number alterations contribute to cancer initiaition, progression therapeutic resistance. Here, we present conceptual framework for examining the patterns human using whole-genome sequencing, whole-exome SNP6 microarray data making it widely applicable diverse datasets. Deploying this 9,873 cancers representing 33 types from TCGA project revealed set 19...
Abstract Background: Cancers with homologous recombination deficiency (HRD) can benefit from platinum salts and PARP inhibitors. Standard diagnostic tests, including FDA-approved companion diagnostics, for detecting HRD require molecular profiling, which is not universally available global testing rates lowest among minority, rural, other underserved populations. Methods: We trained DeepHRD, a deep-learning platform predicting hematoxylin eosin (H&E)-stained histopathological slides,...
Abstract Colorectal cancer (CRC) is the second most frequent cause of cancer-related deaths globally. CRC influenced by colorectal microbiome, which plays a pivotal role in inflammation, DNA damage, and production cancer-promoting metabolites. Most prior microbial studies have identified multiple microbes enriched tumor samples, but these examinations generally focused on from specific country not accounted for patient’s site, sex, diet, or geographical location. Further, interconnection...
Abstract Acquired drug resistance to even the most effective anti cancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired have been identified, underlying molecular mechanisms shaping tumor evolution during treatment are incompletely understood. The extent which therapy actively drives by promoting mutagenic processes or simply provides selective pressure necessary for outgrowth resistant clones open question. Here, we report that lung commonly used...
Abstract Acquired drug resistance to even the most effective anti cancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired have been identified, underlying molecular mechanisms shaping tumor evolution during treatment are incompletely understood. We seen that lung commonly used in clinic induce expression cytidine deaminase APOBEC3A (A3A), leading sustained mutagenesis tolerant cells persisting therapy. Preventing therapy induced A3A by gene deletion...