Obi Lee Griffith

Obi Lee Griffith
Washington University in St. Louis | WUSTL , Wash U · Genome Institute

PhD

About

437
Publications
55,819
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14,583
Citations
Additional affiliations
May 2012 - present
Washington University in St. Louis
Position
  • Professor (Assistant)
January 2011 - present
January 2009 - present

Publications

Publications (437)
Article
Full-text available
The Drug-Gene Interaction database (DGIdb) mines existing resources that generate hypotheses about how mutated genes might be targeted therapeutically or prioritized for drug development. It provides an interface for searching lists of genes against a compendium of drug-gene interactions and potentially 'druggable' genes. DGIdb can be accessed at h...
Article
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Systemic chemotherapy in the adjuvant setting can cure breast cancer in some patients that would otherwise recur with incurable, metastatic disease. However, since only a fraction of patients would have recurrence after surgery alone, the challenge is to stratify high-risk patients (who stand to benefit from systemic chemotherapy) from low-risk pat...
Article
Full-text available
An estimated 4% to 7% of the population will develop a clinically significant thyroid nodule during their lifetime. In many cases, preoperative diagnoses by needle biopsy are inconclusive. Thus, there is a clear need for improved diagnostic tests to distinguish malignant from benign thyroid tumors. The recent development of high-throughput molecula...
Article
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ORegAnno is an open-source, open-access database and literature curation system for community-based annotation of experimentally identified DNA regulatory regions, transcription factor binding sites and regulatory variants. The current release comprises 30 145 records curated from 922 publications and describing regulatory sequences for over 3853 g...
Article
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In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformati...
Article
Introduction: Loss-of-heterozygosity (LOH) events in chromosome 6p, comprising the human leukocyte antigen (HLA) genes, have been reported in about 10% of cutaneous melanoma (compared to 20-40% of squamous cell carcinomas), while copy number gains in this region have been observed in over 50% of melanoma. Recent studies focused in HLA allelic loss...
Article
Neoantigens are tumor-specific peptides on the cell surface that can be recognized by the adaptive immune system. Personalized immunotherapies, such as cancer vaccines, rely on neoantigen prediction to identify sequences that can activate T cells to recognize and destroy the tumor. The majority of cancer vaccine trials have utilized neoantigens der...
Article
Neoantigens are novel peptide sequences resulting from somatic mutations in tumors that upon loading onto major histocompatibility complex (MHC) molecules allow recognition by T cells. Accurate neoantigen identification is thus critical for designing cancer vaccines and predicting response to immunotherapies. Neoantigen identification and prioritiz...
Article
Interpretation of the clinical significance of somatic gene variants in cancer remains a major challenge in cancer diagnosis, prognosis and treatment response prediction. We will report on progress and plans of the Clinical Genome Resource (ClinGen) Somatic Cancer Clinical Domain Working Group (CDWG). The CDWG membership consists of over 150 multi-...
Article
Precision oncology is the practice of interpreting the clinical significance of observed molecular changes in patient neoplasms, potentially impacting medical decision making and care. This process is labor-intensive and (among other challenges) involves accurately translating between variation representation conventions from one resource to the ne...
Article
Childhood cancers present unique challenges for variant interpretation in a clinical context due to their rarity, low mutation burden, diversity of molecular alterations, and heterogeneity among patients. Consequently, genes and variants associated with childhood tumors are under-represented in public cancer databases and knowledgebases. A focused...
Article
The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a publicly accessible resource that aggregates 102,426 gene records and 57,498 drug records from 40 drug-gene interaction data sources to aid both researchers and clinicians in identifying associations between genes of interest and available drugs and therapeutics. By using peer-reviewed...
Article
The Clinical Interpretation of Variants in Cancer (CIViC; www.civicdb.org) knowledgebase is a curation platform designed to capture evidence from the published literature which support or refute the significance of genomic variants in various cancer types. Since the launch of the beta user interface in 2014, this knowledgebase has undergone substan...
Article
As guidelines, therapies and literature on cancer variants expand, the lack of consensus variant interpretations impedes clinical applications. CIViC is a public-domain, crowd-sourced and adaptable knowledgebase of evidence for the clinical interpretation of variants in cancer, designed to reduce barriers to knowledge sharing and alleviate the vari...
Article
Full-text available
Although tobacco use is an independent adverse prognostic feature in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC), the biologic features associated with tobacco use have not been systematically investigated. We characterized genomic and immunologic features associated with tobacco use with whole exome sequencing, mRNA hybridization and immu...
Article
Von Hippel‐Lindau (VHL) disease is a hereditary cancer syndrome where individuals are predisposed to tumor development in the brain, adrenal gland, kidney and other organs. It is caused by pathogenic variants in the VHL tumor suppressor gene. Standardized disease information has been difficult to collect due to the rarity and diversity of VHL patie...
Article
Gene fusions involving the neurotrophic receptor tyrosine kinase genes NTRK1, NTRK2, and NTRK3, are well established oncogenic drivers in a broad range of pediatric and adult tumors. These fusions are also important actionable markers, predicting often dramatic response to FDA approved kinase inhibitors. Accurate interpretation of the clinical sign...
Article
Natural killer (NK) cells are innate lymphoid cells that eliminate cancer cells, produce cytokines, and are being investigated as a nascent cellular immunotherapy. Impaired NK cell function, expansion, and persistence remain key challenges for optimal clinical translation. One promising strategy to overcome these challenges is cytokine-induced memo...
Preprint
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Personalized cancer vaccines designed to target neoantigens represent a promising new treatment paradigm in oncology. In contrast to classical idiotype vaccines, we hypothesized that polyvalent vaccines could be engineered for the personalized treatment of follicular lymphoma (FL) using neoantigen discovery by combined whole exome sequencing (WES)...
Article
Background: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%-20% of patients and underpinnings of resistance remain undefined. Methods: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was...
Preprint
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Background Liver cancer is the second leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) risk factors include chronic hepatitis, cirrhosis, and alcohol abuse, whereby tumorigenesis is induced through inflammation and subsequent fibrotic response. However, a subset of HCC arises in non-cirrhotic livers. We characterized...
Article
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In cancer, missense mutations in the DNA-binding domain of TP53 are common. They abrogate canonical p53 activity and frequently confer gain-of-oncogenic function (GOF) through localization of transcriptionally active mutant p53 to noncanonical genes. We found that several recurring p53 mutations exhibit a sex difference in frequency in patients wit...
Article
Pediatric and young adult (YA) patients with acute myeloid leukemia (AML) who relapse after allogeneic hematopoietic cell transplantation (HCT) have extremely poor prognosis. Standard salvage chemotherapy and donor lymphocyte infusions (DLI) have little curative potential. Previous studies showed that natural killer (NK) cells can be stimulated ex...
Article
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Allogeneic cancer vaccines are designed to induce antitumor immune responses with the goal of impacting tumor growth. Typical allogeneic cancer vaccines are produced by expansion of established cancer cell lines, transfection with vectors encoding immunostimulatory cytokines, and lethal irradiation. More than 100 clinical trials have investigated t...
Article
New therapies are needed for patients with relapsed/refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL) who do not benefit from or are ineligible for stem cell transplant and chimeric antigen receptor therapy. The CD30-targeted antibody-drug conjugate brentuximab vedotin (BV) and the immunomodulator lenalidomide (Len) have demonstrated promi...
Article
Clinical significance of somatic gene variants needs to be comprehensively characterized for their diagnostic, prognostic and/or therapeutic actionability in patient management. However, challenges remain due to discrepancies in interpretation and reporting of these somatic variants among different testing labs. Therefore, standardized curation, cl...
Article
Natural killer (NK) cells are innate lymphoid cells that mediate anti-tumor responses and exhibit innate memory following stimulation with IL-12, IL-15, and IL-18, thereby differentiating into cytokine-induced memory-like (ML) NK cells. ML NK cells have well-described enhanced anti-tumor properties; however, the molecular mechanisms underlying thei...
Article
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Maximizing the personal, public, research, and clinical value of genomic information will require the reliable exchange of genetic variation data. We report here the Variation Representation Specification (VRS, pronounced “verse”), an extensible framework for the computable representation of variation that complements contemporary human-readable an...
Article
Full-text available
The creation of visualizations to interpret genomics data remains an important aspect of data science within computational biology. The GenVisR Bioconductor package was created to lower the entry point for publication‐quality graphics and has remained a popular suite of tools within this domain. GenVisR supports visualizations covering a breadth of...
Article
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Purpose Patients with triple-negative breast cancer (TNBC) who do not achieve pathological complete response (pCR) following neoadjuvant chemotherapy have a high risk of recurrence and death. Molecular characterization may identify patients unlikely to achieve pCR. This neoadjuvant trial was conducted to determine the pCR rate with docetaxel and ca...
Preprint
Full-text available
Bam-readcount is a utility for generating low-level information about sequencing data at specific nucleotide positions. Originally designed to help filter genomic mutation calls, the metrics it outputs are useful as input for variant detection tools and for resolving ambiguity between variant callers . In addition, it has found broad applicability...
Article
Full-text available
Bam-readcount is a utility for generating low-level information about sequencing data at specific nucleotide positions. Originally designed to help filter genomic mutation calls, the metrics it outputs are useful as input for variant detection tools and for resolving ambiguity between variant callers . In addition, it has found broad applicability...
Preprint
The malignant Hodgkin and Reed Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) are scarce in affected lymph nodes, creating a challenge to detect driver somatic mutations. As an alternative to cell purification techniques, we hypothesized that ultra-deep exome sequencing would allow genomic study of HRS cells, thereby streamlining analysi...
Conference Paper
p>Despite the well-established role of recurrent gene fusions as oncogenic drivers, current practices for characterizing and interpreting gene fusion events in clinical testing and in biomedical literature are inconsistent. From the conceptual definition of gene fusions to the salient elements that characterize these alterations, a lack of communit...
Conference Paper
CIViC (civicdb.org) is an open access, expertly moderated knowledgebase for crowdsourcing Clinical Interpretations of Variants in Cancer. Stakeholders globally-including those in government, academia, industry and medicine-use CIViC to find and curate actionable interpretations of genomic variants in their therapeutic, prognostic, predisposing, dia...
Preprint
Full-text available
Background Spontaneous cancers in companion dogs are increasingly recognized as robust models of human disease. This recognition has led to translational clinical trials in companion dogs with osteosarcoma, lymphoma, melanoma, squamous cell carcinoma, and soft tissue sarcoma. The ability to precisely track tumor-specific immune responses in such cl...
Preprint
Full-text available
CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capabil...
Preprint
Full-text available
The tumor suppressor TP53 is the most frequently mutated gene in cancer. Most TP53 mutations are missense mutations in the DNA-binding domain, which in addition to loss of canonical p53 activity, frequently confer gain-of-function (GOF) aberrant transcriptional activity through mutant p53 localization to non-canonical genes. GOF phenotypes differ b...
Article
Full-text available
Brain and central nervous system tumors are the most common form of solid tumor cancers and the second most common cancer overall among children. While many advances have been made in understanding the genomics of childhood brain tumors in recent years, the role of copy number alterations (CNAs) has not been fully characterized. Although the genome...
Article
Introduction: Effective colorectal cancer (CRC) prevention and screening requires sensitive detection of all advanced neoplasias (CRC and advanced adenomas [AA]). However, existing noninvasive screening approaches cannot accurately detect adenomas with high sensitivity. Methods: Here, we describe a multifactor assay (RNA-FIT test) that combines...
Article
Purpose: N-803 is an IL-15 receptor superagonist complex, designed to optimize in vivo persistence and trans-presentation, thereby activating and expanding natural killer (NK) cells and CD8+ T cells. Monoclonal antibodies (mAb) direct FcR-bearing immune cells, including NK cells, to recognize and eliminate cancer targets. The ability of IL-15R ago...
Preprint
Purpose: Tobacco use is an independent adverse prognostic feature in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Despite this, the biologic features associated with tobacco use have not been systematically investigated in this population. We sought to characterize the genomic and immunologic features of HPV(...
Article
Carrot-Zhang and colleagues describe associations between Native American ancestry and the somatic mutational landscape in lung cancer, including tumor mutation burden and specific driver mutations in EGFR, KRAS, and STK11. Local ancestry analysis suggests that specific germline loci, and not environment, underlie these associations.
Conference Paper
p> Background : Triple negative breast cancer (TNBC) has a marked molecular diversity that promotes clinical heterogeneity. Less than 40% of TNBC patients will achieve a pathological complete response (pCR) to standard neoadjuvant chemotherapy. Patients who do not achieve pCR have a high risk of disease recurrence and subsequent death from breast c...
Article
Full-text available
Osteosarcoma is a rare disease in children but is one of the most common cancers in adult large breed dogs. The mutational landscape of both the primary and pulmonary metastatic tumor in two dogs with appendicular osteosarcoma (OSA) was comprehensively evaluated using an automated whole genome sequencing, exome and RNA-seq pipeline that was adapted...
Article
Purpose: In a head and neck squamous cell carcinoma (HNSCC) "window of opportunity" clinical trial, we reported that trametinib reduced MEK-Erk1/2 activation and resulted in tumor responses in a subset of patients. Here, we investigated resistance to trametinib and molecular correlates in HNSCC cell lines and patient samples. Experimental design:...
Article
25 Background: Effective colorectal cancer (CRC) prevention and screening requires sensitive detection of all advanced neoplasias (colorectal cancer and advanced adenomas). Existing noninvasive screening approaches cannot accurately detect precancerous adenomas with high sensitivity. Here we describe a multi-factor assay (RNA-FIT test) that combine...
Preprint
Full-text available
Maximizing the personal, public, research, and clinical value of genomic information will require that clinicians, researchers, and testing laboratories exchange genetic variation data reliably. Developed by a partnership among national information resource providers, public initiatives, and diagnostic testing laboratories under the auspices of the...
Article
PURPOSE Physicians treating hematologic malignancies increasingly order targeted sequencing panels to interrogate recurrently mutated genes. The precise impact of these panels on clinical decision making is not well understood. METHODS Here, we report our institutional experience with a targeted 40-gene panel (MyeloSeq) that is used to generate a...
Preprint
Full-text available
Neoantigens are novel peptide sequences resulting from somatic mutations in tumors that upon loading onto major histocompatibility complex (MHC) molecules allow recognition by T cells. Accurate neoantigen identification is thus critical for designing cancer vaccines and predicting response to immunotherapies. Neoantigen identification and prioritiz...
Article
Full-text available
The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that provides information on drug-gene interactions and druggable genes from publications, databases, and other web-based sources. Drug, gene, and interaction data are normalized and merged into conceptual groups. The information contained in this resource is available to u...
Article
Multiple Myeloma (MM) is a malignancy of plasma cells that affects over 30,000 Americans every year. Despite advances in the treatment of the disease, approximately 12,000 American patients will still die of MM in 2019. One of the mainstays of treatment for MM is the immunomodulatory and antiangiogenic drug lenalidomide; which is used in induction...
Conference Paper
Purpose/Background: cHL patients who receive standard therapy have a high rate of event-free and overall survival. However, some patients (~10%) will be refractory to initial therapy and up to 1/3 will relapse. Thus, improved methods of prognostication and new treatment targets are needed. High-throughput sequencing can identify recurrent somatic m...
Article
Full-text available
Although endometrial cancer is the most common cancer of the female reproductive tract, we have little understanding of what controls endometrial cancer beyond the transcriptional effects of steroid hormones such as estrogen. As a result, we have limited therapeutic options for the ~62,000 women diagnosed with endometrial cancer each year in the Un...
Preprint
Full-text available
The Drug-Gene Interaction Database (DGIdb, www.dgidb.org ) is a web resource that provides information on drug-gene interactions and druggable genes from various sources including publications, databases, and other web-based sources in one resource. These drug, gene, and interaction claims are normalized and grouped to identify aliases, merge conce...
Conference Paper
p>Gliomas originate from neuroglial progenitor cells in the brain or spinal cord and have an incidence of ~6 cases per 100,000 individuals each year in the United States. Approximately half of glioma cases present as an aggressive type of astrocytoma known as glioblastoma multiforme (GBM). Due to its location and diffuse morphology, GBM has only a...
Conference Paper
Full-text available
The use of clinical gene sequencing is now commonplace, and genome analysts and molecular pathologists are often tasked with the labor-intensive process of interpreting the clinical significance of large numbers of tumor variants. Numerous independent knowledgebases have been constructed to alleviate this manual burden, however these knowledgebases...