A5011957277- Cancer Immunotherapy and Biomarkers
- Radiomics and Machine Learning in Medical Imaging
- Colorectal and Anal Carcinomas
- Inflammatory Biomarkers in Disease Prognosis
- Esophageal Cancer Research and Treatment
- Cancer Genomics and Diagnostics
- Multiple and Secondary Primary Cancers
- Lung Cancer Research Studies
- Bladder and Urothelial Cancer Treatments
- Lung Cancer Treatments and Mutations
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Treatments and Studies
- Fibroblast Growth Factor Research
- Immune Cell Function and Interaction
- Protein Structure and Dynamics
- Bioinformatics and Genomic Networks
- Lymphoma Diagnosis and Treatment
- Computational Drug Discovery Methods
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Genetic factors in colorectal cancer
- HER2/EGFR in Cancer Research
- Kruppel-like factors research
- Renal cell carcinoma treatment
- Machine Learning in Bioinformatics
Thermo Fisher Scientific (United States)
2018-2020
Michigan United
2013
University of Michigan
2007-2013
Michigan Center for Translational Pathology
2013
Howard Hughes Medical Institute
2013
National Health Research Institutes
2013
Comprehensive Blood & Cancer Center
2013
Chang Gung University
2013
U-M Rogel Cancer Center
2013
Washtenaw Community College
2011
Abstract Through a prospective clinical sequencing program for advanced cancers, four index cases were identified which harbor gene rearrangements of FGFR2, including patients with cholangiocarcinoma, breast cancer, and prostate cancer. After extending our assessment FGFR across multiple tumor cohorts, we additional fusions intact kinase domains in lung squamous cell bladder thyroid oral glioblastoma, head neck All fusion partners tested exhibit oligomerization capability, suggesting shared...
Binding MOAD (Mother of All Databases) is a database 9836 protein–ligand crystal structures. biologically relevant ligands are annotated, and experimental binding-affinity data reported when available. has almost doubled in size since it was originally introduced 2004, demonstrating steady growth with each annual update. Several technologies, such as natural language processing, help drive this constant expansion. Along increasing data, improved usability. The website now showcases faster,...
A major goal in drug design is the improvement of computational methods for docking and scoring. The Community Structure Activity Resource (CSAR) aims to collect available data from industry academia which may be used this purpose (www.csardock.org). Also, CSAR charged with organizing community-wide exercises based on collected data. first these was aimed gauge overall state scoring, using a large diverse set protein–ligand complexes. Participants were asked calculate affinity complexes as...
Abstract Background Anti-PD-1 and PD-L1 (collectively PD-[L]1) therapies are approved for many advanced solid tumors. Biomarkers beyond immunohistochemistry, microsatellite instability, tumor mutation burden (TMB) may improve benefit prediction. Methods Using treatment data genomic transcriptomic tissue profiling from an observational trial (NCT03061305), we developed Immunotherapy Response Score (IRS), a pan-tumor predictive model of PD-(L)1 benefit. IRS real-world progression free survival...
The residue composition of a ligand binding site determines the interactions available for diffusion-mediated binding, and understanding general these sites is great importance if we are to gain insight into functional diversity proteome. Many structure-based drug design methods utilize such heuristic information improving prediction or characterization ligand-binding in proteins unknown function. Binding MOAD database one largest curated sets protein-ligand complexes, provides source...
Physical differences in small molecule binding between enzymes and nonenzymes were found through mining the protein-ligand database, Binding MOAD (Mother of All Databases). The data suggest that divergent approaches may be more productive for improving affinity ligands two classes proteins. High-affinity are much larger than those with low affinity, indicating addition complementary functional groups is likely to improve an enzyme inhibitor. However, this process not as fruitful nonenzymes....
Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PD-L1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 were included assigned IRS-High (-H) versus -Low (-L) groups. Associations real-world progression-free survival (rwPFS) overall (OS) determined by Cox proportional hazards (CPH) modeling. Those...
467 Background: Angiogenesis inhibitors, including vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs), are standard of care therapy (alone and in combination) for several advanced cancers, RCC. There is an unmet need a biomarker to identify patients with RCC most likely benefit from VEGFR TKIs guide individualized treatment decision making. Hence, we sought develop validate predicting single-agent systemic TKI Methods: Candidate biomarkers were selected by...
Abstract The lack of standardized methods for human phenotyping is a major obstacle in translational science. We have developed bleeding history system comprising an ontology, questionnaire, Web‐based phenotype recording instrument (PRI), and database. ontology facilitates transparency, collaboration, aggregation data, data analysis. integrated allows investigators worldwide to use the PRI, add their de‐identified database, query aggregated data. Thus, this can increase power detect...
Abstract An appropriate structural superposition identifies similarities and differences between homologous proteins that are not evident from sequence alignments alone. We have coupled our Gaussian‐weighted RMSD (wRMSD) tool with a aligner seed extension (SE) algorithm to create robust technique for overlaying structures aligning sequences of (HwRMSD). HwRMSD overcomes errors in the initial alignment would normally propagate into standard overlay. SE can generate corrected improved obtained...
ADVERTISEMENT RETURN TO ISSUEPREVErratumNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to CSAR Benchmark Exercise of 2010: Selection the Protein–Ligand ComplexesJames B. Dunbar, Jr.*, Richard D. Smith, Chao-Yie Yang, Peter Man-Un Ung, Katrina W. Lexa, Nickolay A. Khazanov, Jeanne Stuckey, Shaomeng Wang, and Heather Carlson*Cite this: J. Chem. Inf. Model. 2011, 51, 9, 2146Publication Date (Web):August 19, 2011Publication History Published online19 August 2011Published inissue 26...
Abstract The MAPK and PI3K pathways are frequently altered in human cancer targeted by dozens of agents clinical trials. successful application these therapies, alone or combination, may depend on the activation status both pathways. Next-generation sequencing exomes provides a unique opportunity to systematically survey pathway alterations cancer. Using somatic mutation data obtained from Cancer Genome Atlas, we sought catalog members with driver mutations, frequency occurrence common...
Abstract Despite the recent clinical success of antibody drug conjugates (ADC) in oncology, predictive biomarkers are lacking, potentially limiting their impact. Herein, we evaluated ability candidate alone and combination to predict objective response rates observed solid tumor patients treated with TROP2-targeted ADC, sacituzumab govitecan (SG), as determined IMMU-12-01 basket trial. We leveraged available next generation sequencing (NGS)-based molecular profiling data from an independent...
473 Background: By predicting those most likely to relapse, cfDNA-based MRD testing has potential clinical utility for adjuvant therapy decision making. Ideally, would be paired with validated treatment selection enable precision therapy. Herein we report the development and application of a combined personalized test patients GU cancer. Methods: Patients clinically localized solid tumors undergoing definitive were enrolled on prospective trial (NCT05082701) where was performed standard...
Abstract Background: In non-small cell lung cancer (NSCLC), the MET tyrosine kinase receptor can be mutated or amplified resulting in dysregulation of function leading to tumor proliferation. exon 14 (METEx14) and NSCLC tumors have shown varied response immunotherapy. Therefore, we sought compare genomic immune landscape MET-altered NSCLC. Methods: The profiles 3,821 sequenced using Strata Select assay on Oncology Platform were analyzed. Tumors sorted based METex14 mutations, amplification...
Abstract Background: Antibody-drug conjugates (ADCs), including trastuzumab deruxtecan (T-DXd; targeting HER2) and sacituzumab govitecan (SG; TROP2), have transformed the management of metastatic breast cancer, with additional ADCs approved in other solid tumors or late-stage development. To date, expression ADC target alone has been poorly predictive objective response rates (ORRs) both cancer tumors. Hence, there is an urgent need to develop better biomarkers guide vs. treatments, T-DXd SG...
Binding MOAD (Mother of All Databases) is the largest collection high-quality, protein-ligand complexes available from Protein Data Bank. It has grown to 9837 hand-curated entries. Here, we describe our semi-annual updating procedures and BUDA (Binding Unstructured Analysis), a custom workflow tool that incorporates natural language processing technologies facilitate annotation process.
Abstract Patients with chromosomal rearrangements resulting in fusion proteins are amongst the most responsive to targeted therapy. For example, targeting of BCR-ABL chronic myelogenous leukemia (CML) imatinib and EML4-ALK non-small cell lung cancer (NSCLC) crizotinib has led dramatic patient responses these diseases. While is approved for use positive NSCLC through its inhibition ALK, drug also inhibits ROS1, MST1R (RON), MET, more recently been shown inhibit ALK homolog, LTK. To gain a...
Abstract Gene fusions encode oncogenic drivers in hematological and solid tumors are often associated with dramatic clinical responses the appropriate targeted agents. In principle, massively parallel paired-end sequencing can identify structural rearrangements tumor genomes transcriptomes. However, computational methods to gene varied, still evolving largely trained on cell line data. We sought develop systematic characterize known discover novel cancer. RNASeq data for approximately 3,400...
Abstract Trastuzumab deruxtecan (Enhertu) is effective in "HER2 Low" breast cancer, defined by 1+ or 2+ expression immunohistochemistry (IHC). Interest has now turned toward defining a sub-population of IHC 0+ tumors that may have HER2 below the limit detection/quantification and thus also be responsive. We previously validated high dynamic range RNA assay run as part our comprehensive genomic profiling test, StrataNGS. Herein, we evaluated data together with copy number clinical outcome...
Abstract Background: We previously reported the development and validation of an integrative Immunotherapy Response Score (IRS) algorithm, which integrates tumor mutation burden (TMB) quantitative gene expression PD-L1, PD-1, ADAM12 TOP2A, to predict PD-1 or PD-L1 (together PD-[L]1) monotherapy (mono) benefit across solid tumors from routine formalin fixed paraffin embedded samples. Herein, we evaluated IRS performance for predicting pembrolizumab (pembro) mono in a second, independent...