- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Fuel Cells and Related Materials
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Nuclear and radioactivity studies
- Hepatitis C virus research
- PARP inhibition in cancer therapy
- Genomics and Rare Diseases
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- Biomedical Text Mining and Ontologies
- Gene expression and cancer classification
- Protein Structure and Dynamics
- Advanced biosensing and bioanalysis techniques
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Advanced Text Analysis Techniques
- Topic Modeling
- Computational Drug Discovery Methods
- Genetic factors in colorectal cancer
- Enzyme Structure and Function
- Biochemical and Molecular Research
Tempus Labs (United States)
2018-2025
National Institute of Standards and Technology
2015-2018
Material Measurement Laboratory
2015
Stanford University
2015
University of California, San Diego
2005-2013
Memorial Sloan Kettering Cancer Center
2011
Texas A&M University
2005
We developed and clinically validated a hybrid capture next generation sequencing assay to detect somatic alterations microsatellite instability in solid tumors hematologic malignancies. This targeted oncology utilizes tumor-normal matched samples for highly accurate alteration calling whole transcriptome RNA unbiased identification of gene fusion events. The was with combination clinical specimens cell lines, recorded sensitivity 99.1% single nucleotide variants, 98.1% indels, 99.9%...
Abstract Background Homologous recombination deficiency (HRD) is a phenotype that characterized by the inability of cell to effectively repair DNA double-strand breaks using homologous (HRR) pathway. Loss-of-function genes involved in this pathway can sensitize tumors poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy, which target destruction cancer cells working concert with HRD through synthetic lethality. However, identify patients these...
The three-dimensional structures of noncoding RNA molecules reveal recurring architectural motifs that have been exploited for the design artificial nanomaterials. Programmed assembly nanoobjects from autonomously folding tetraloop-receptor complexes as well junction has achieved previously through sequence-directed hybridization complex sets long oligonucleotides. Due to size and complexity, structural characterization limited low-resolution microscopy studies. Here we present design,...
Abstract Many applications require a method for translating large list of bond angles and lengths to precise atomic Cartesian coordinates. This simple but computationally consuming task occurs ubiquitously in modeling proteins, DNA, other polymers as well many fields such robotics. To find an optimal method, algorithms can be compared by number operations, speed, intrinsic numerical stability, parallelization. We discuss five established methods growing protein backbone serial chain...
Highly multiplexed assays for quantitation of RNA transcripts are being used in many areas biology and medicine. Using data generated by these transcriptomic requires measurement assurance with appropriate controls. Methods to prototype evaluate multiple controls were developed as part the External Controls Consortium (ERCC) assessment process. These approaches included a modified Latin square design provide broad dynamic range relative abundance known differences between four complex pools...
We have developed a clinically validated NGS assay that includes tumor, germline and RNA sequencing. apply this to clinical specimens cell lines, we demonstrate sensitivity of 98.4% positive predictive value 100% for the actionable variants measured by assay. also highly accurate copy number measurements gene rearrangement identification.
Importance The National Comprehensive Cancer Network (NCCN) guidelines for non–small cell lung cancer suggest that RNA next-generation sequencing (NGS) may improve the detection of fusions and splicing variants compared with DNA-NGS alone. However, there is limited adoption RNA-NGS in routine oncology clinical care today. Objective To analyze evidence from a diverse cohort patients advanced adenocarcinoma compare NCCN-recommended actionable structural (aSVs; variants) via concurrent DNA vs...
DAPper ligands: The 3,5-diaminopiperidine (DAP) heterocycle has been developed as a structural mimetic of the RNA-recognizing pharmacophore 2-DOS scaffold. Here we describe synthesis novel modular DAP ligands that bind to conformational target in internal ribosome entry site RNA hepatitis C virus. Detailed facts importance specialist readers are published "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please...
Abstract Introduction: The xT tumor-normal matched assay, which sequences solid tumor biopsy paired with buffy coat, has enabled the accumulation of large amounts clonal hematopoiesis (CH) data. Although buffy-coat sequencing is gold standard for distinguishing from non-tumor variants, accurately identifying CH variants and them germline or artifactual presents unique algorithmic challenges. coat sequenced at lower depth than tumor, potentially impacting accuracy variant calling low allele...
Oligonucleotide models of ribosomal RNA domains are powerful tools to study the binding and molecular recognition antibiotics that interfere with bacterial translation. Techniques such as selective chemical modification, fluorescence labeling mutations cumbersome for whole ribosome but readily applicable model RNAs, which crystallized often give rise higher resolution crystal structures suitable detailed analysis ligand–RNA interactions. Here, we have investigated HX construct contains two...
Genome-scale "-omics" measurements are challenging to benchmark due the enormous variety of unique biological molecules involved. Mixtures previously-characterized samples can be used repeatability and reproducibility using component proportions as truth for measurement. We describe evaluate experiments characterizing performance RNA-sequencing (RNA-Seq) measurements, discuss cases where mixtures serve effective process controls.We apply a linear model total RNA mixture in RNA-seq...
3077 Background: While targeted DNA-seq can detect clinically actionable fusions in tumor tissue samples, technical and analytical challenges may give rise to false negatives. RNA-based, whole-exome sequencing provides a complementary method for fusion detection, improve the identification of variants. In this study, we quantify benefit using large, real-world clinical dataset assess detected from RNA conjunction with DNA profiling. Methods: Using Tempus Research Database, retrospectively...
The potential utility of microRNA as biomarkers for early detection cancer and other diseases is being investigated with genome-scale profiling differentially expressed microRNA. Processes measurement assurance are critical components measurements. Here, we evaluated the a set total RNA samples, designed between-sample differences in relative abundance miRNAs, process controls. Three pure human samples (brain, liver, placenta) two different mixtures these were control on multiple systems at...
Abstract Tumor genome sequencing has emerged as a powerful tool for identifying biomarkers targeted cancer therapies. While DNA is well-established method and considered gold standard, RNA (RNA-seq) can identify anomalies in gene transcription, regulation of expression, fusions, which have critical diagnostic therapeutic impacts. Tempus Labs CLIA-certified, CAP-accredited offers several clinically validated NGS assays solid tumor hematological malignancy testing, including the xT 648-gene...
Abstract Homologous recombination deficiency (HRD) assays determine patient eligibility for treatment with PARP inhibitors and other DNA repair targeting drugs; therefore, understanding variability in how these measure report HRD is critical patients providers. various factors to status including causes (i.e., inactivation HR pathway genes) consequences genomic scarring). Methodological across has led a suggestion that the may not agree on per basis. An empirical assessment of assay guide...
Genome-scale ?-omics? measurements are challenging to benchmark due the enormous variety of unique biological molecules involved. Mixtures previously-characterized samples can be used repeatability and reproducibility using component proportions as truth for measurement. We describe evaluate experiments characterizing performance RNA-sequencing (RNA-Seq) measurements, discuss cases where mixtures serve effective process controls. apply a linear model total RNA mixture in RNA-seq experiments....