Philip Bourne

Philip Bourne
National Institutes of Health | NIH · NIH Office of the Director (OD)

PhD

About

494
Publications
95,672
Reads
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36,011
Citations
Additional affiliations
March 2014 - present
National Institutes of Health
Position
  • Associate Director for Data Science
January 2000 - February 2014
University of California, San Diego
Position
  • Associate Vice Chancellor & Professor
March 1995 - February 2014
San Diego Supercomputer Center
Position
  • Advisor

Publications

Publications (494)
Article
Full-text available
The biomedical research community is investing heavily in biomedical cloud platforms. Cloud computing holds great promise for addressing challenges with big data and ensuring reproducibility in biology. However, despite their advantages, cloud platforms in and of themselves do not automatically support FAIRness. The global push to develop biomedica...
Article
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Special sessions are important parts of scientific meetings and conferences: They gather together researchers and students interested in a specific topic and can strongly contribute to the success of the conference itself. Moreover, they can be the first step for trainees and students to the organization of a scientific event. Organizing a special...
Preprint
Unresolved questions about the discrete/continuous dichotomy of protein fold space permeate structural and evolutionary biology. From protein structure comparison and classification to evolutionary analyses and function prediction, our views of fold space implicitly rest upon many assumptions that impact how we analyze, interpret and come to unders...
Preprint
Determining protein-ligand interaction characteristics and mechanisms is critical in the drug discovery process. Here we review recent progress and successful applications of a systematic protein-ligand interaction fingerprint (IFP) approach for investigating proteome-wide protein-ligand interactions for drug development. Specifically, we review th...
Article
As efforts advance around the globe, the US falls behind
Preprint
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On August 2, 2021 a group of concerned scientists and US funding agency and federal government officials met for an informal discussion to explore the value and need for a well-coordinated US Open Research Commons (ORC); an interoperable collection of data and compute resources within both the public and private sectors which are easy to use and ac...
Article
Determining protein–ligand interaction characteristics and mechanisms is crucial to the drug discovery process. Here, we review recent progress and successful applications of a systematic protein–ligand interaction fingerprint (IFP) approach for investigating proteome-wide protein–ligand interactions for drug development. Specifically, we review th...
Article
Full-text available
Communication is a fundamental part of scientific development and methodology. With the advancement of the internet and social networks, communication has become rapid and sometimes overwhelming, especially in science. It is important to provide scientists with useful, effective, and dynamic tools to establish and build a fluid communication framew...
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Background: Reactivation of the varicella-zoster virus (VZV), which causes herpes zoster (HZ, synonym: shingles) in humans, can be a rare adverse reaction to vaccines. Recently, reports of cases after COVID-19 vaccination have arisen. Objectives: The aim of this study was to assess if the frequency of HZ is found to increase after COVID-19 vacci...
Article
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Background: The COVID-19 pandemic is being battled via the largest vaccination campaign in history, with more than eight billion doses administered thus far. Therefore, discussions about potentially adverse reactions, and broader safety concerns, are critical. The U.S. Vaccination Adverse Event Reporting System (VAERS) has recorded vaccination side...
Preprint
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Advances in biomedicine are largely fueled by exploring uncharted territories of human biology. Machine learning can both enable and accelerate discovery, but faces a fundamental hurdle when applied to unseen data with distributions that differ from previously observed ones -- a common dilemma in scientific inquiry. We have developed a new deep lea...
Chapter
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Kinase-targeted drug design is challenging. It requires designing inhibitors that can bind to specific kinases, when all kinase catalytic domains share a common folding scaffold that binds ATP. Thus, obtaining the desired selectivity, given the whole human kinome, is a fundamental task during early-stage drug discovery. This begins with deciphering...
Article
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This Perspective examines a recent surge of information regarding the potential benefits of acid-suppression drugs in the context of COVID-19, with a particular eye on the great variability (and, thus, confusion) that has arisen across the reported findings, at least as regards the popular antacid famotidine. The degree of inconsistency and discord...
Preprint
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Background: Numerous clinical trials have considered the potential linkages between statins and cancer. Despite some evidence for reduced mortality associated with statin use, the results thus far have been somewhat inconclusive and not easily comparable, thus hampering the emergence of a consensus. We suspect that this uncertainty would be reduced...
Article
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Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here we report that elevated interleukin-13 (IL-13) was associated with the need for mechanical ventilation in two independent patient c...
Preprint
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Reversible covalent kinase inhibitors (RCKIs) are a class of novel kinase inhibitors attracting increasing attention because they simultaneously show the selectivity of covalent kinase inhibitors, yet avoid permanent protein-modification-induced adverse effects. Over the last decade, RCKIs have been reported to target different kinases, including a...
Preprint
Full-text available
Kinase-targeted drug design is challenging. It requires designing inhibitors that can bind to specific kinases when all kinase catalytic domains share a common folding scaffold that binds ATP. Thus, obtaining the desired selectivity, given the whole human kinome, is a fundamental task during early-stage drug discovery. This begins with deciphering...
Preprint
Full-text available
We consider the recent surge of information on the potential benefits of acid-suppression drugs in the context of COVID-19, with an eye on the variability (and confusion) across the reported findings--at least as regards the popular antacid famotidine. The inconsistencies reflect contradictory conclusions from independent clinical-based studies tha...
Preprint
Full-text available
COVID-19 has spurred much interest in the therapeutic potential of repurposed drugs. A family of acid-reducing drugs, known as histamine H2 receptor antagonists (H2RA), competitively bind the H2R and block its stimulation by histamine; examples of such drugs are famotidine (e.g., Pepcid) and ranitidine (e.g., Zantac). A dense web of functionalities...
Preprint
Full-text available
COVID-19 has spurred much interest in the therapeutic potential of repurposed drugs, such as acid-reducing drugs that act as histamine H2 receptor antagonists (H2RA). These compounds, exemplified by famotidine (e.g., Pepcid) and ranitidine (e.g., Zantac), bind the H2R and block the histamine-triggered stimulation of signal transduction cascades. Hi...
Article
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Why would a computational biologist with 40 years of research experience say bioinformatics is dead? The short answer is, in being the Founding Dean of a new School of Data Science, what we do suddenly looks different.
Article
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The rapidly developing pandemic, known as coronavirus disease 2019 (COVID-19) and caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently spread across 213 countries and territories. This pandemic is a dire public health threat—particularly for those suffering from hypertension, cardiovascular diseases, pulmonary di...
Article
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Background Given that an individual’s age and gender are strongly predictive of coronavirus disease 2019 (COVID-19) outcomes, do such factors imply anything about preferable therapeutic options? Methods An analysis of electronic health records for a large (68,466-case), international COVID-19 cohort, in 5-year age strata, revealed age-dependent se...
Preprint
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BACKGROUND Given that an individual's age and gender are strongly predictive of COVID-19 outcomes, do such factors imply anything about preferable therapeutic options? METHODS An analysis of electronic health records for a large (68,466-case), international COVID-19 cohort, in five-year age strata, revealed age-dependent sex differences. In particu...
Chapter
Research on kinase-targeting drugs has made great strides over the last 30 years and is attracting greater attention for the treatment of yet more kinase-related diseases. Currently, 42 kinase drugs have been approved by the FDA, most of which (Wilson et al., Cancer Research 78(1):15–29, 2018) are Type I/II inhibitors. Notwithstanding these advance...
Preprint
These Ten Simple Rules (TSR) aim primarily at individuals in their late teenage years--late high school (LHS) or early college (EC)--who are either considering or actively searching for a first research opportunity in a university lab. The Rules are motivated by empirical observations and our own experiences. First, and most immediately and practic...
Article
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Background: Despite decades of research and interventions, significant health disparities persist. Seventeen years is the estimated time to translate scientific discoveries into public health action. This Narrative Review argues that the translation process could be accelerated if representative data were gathered and used in more innovative and ef...
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Overview We suspect that there is a level of granularity of protein structure intermediate between the classical levels of ‘architecture’ and ‘topology’, as reflected in such phenomena as extensive 3D structural similarity above the level of (super)folds. Here, we examine this notion of architectural identity despite topological variability, starti...
Preprint
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The biological function of a protein stems from its 3-dimensional structure, which is thermodynamically determined by the energetics of interatomic forces between its amino acid building blocks (the order of amino acids, known as the sequence, defines a protein). Given the costs (time, money, human resources) of determining protein structures via e...
Article
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Many proteins fold into highly regular and repetitive three dimensional structures. The analysis of structural patterns and repeated elements is fundamental to understand protein function and evolution. We present recent improvements to the CE-Symm tool for systematically detecting and analyzing the internal symmetry and structural repeats in prote...
Article
The small β-barrel (SBB) is an ancient protein structural domain characterized by extremes: it features a broad range of structural varieties, a deeply intricate evolutionary history, and it is associated with a bewildering array of cellular pathways. Here, we present a thorough, survey-based analysis of the structural properties of SBBs. We first...
Preprint
Full-text available
Many proteins fold into highly regular and repetitive three dimensional structures. The analysis of structural patterns and repeated elements is fundamental to understand protein function and evolution. We present recent improvements to the CE-Symm tool for systematically detecting and analyzing the internal symmetry and structural repeats in prote...
Article
Full-text available
Data science has emerged from the proliferation of digital data, coupled with advances in algorithms, software and hardware (e.g., GPU computing). Innovations in structural biology have been driven by similar factors, spurring us to ask: can these two fields impact one another in deep and hitherto unforeseen ways? We posit that the answer is yes. N...
Preprint
Full-text available
Data science has emerged from the proliferation of digital data, coupled with advances in algorithms, software and hardware (e.g., GPU computing). Innovations in structural biology have been driven by similar factors, spurring us to ask: can these two fields impact one another in deep and hitherto unforeseen ways? We posit that the answer is yes. N...
Article
Full-text available
Biomedical research has become a digital data–intensive endeavor, relying on secure and scalable computing, storage, and network infrastructure, which has traditionally been purchased, supported, and maintained locally. For certain types of biomedical applications, cloud computing has emerged as an alternative to locally maintained traditional comp...
Preprint
Full-text available
The small β-barrel is an ancient protein structural domain characterized by extremes: It features an extremely broad range of structural varieties, a deeply intricate evolutionary history, and it is associated with a bewildering array of biomolecular pathways and physiological functions. These and related features of this domain are described and a...
Article
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With reduced risk of toxicity and high selectivity, covalent small-molecule kinase inhibitors (CSKIs) have emerged rapidly. Through the lens of structural system pharmacology, here we review this rapid progress by considering design strategies and the challenges and opportunities offered by current CSKIs.
Article
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The Open Science Prize was established with the following objectives: first, to encourage the crowdsourcing of open data to make breakthroughs that are of biomedical significance; second, to illustrate that funders can indeed work together when scientific interests are aligned; and finally, to encourage international collaboration between investiga...
Article
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This article describes efforts at the National Institutes of Health (NIH) from 2013 to 2016 to train a national workforce in biomedical data science. We provide an analysis of the Big Data to Knowledge (BD2K) training program strengths and weaknesses with an eye toward future directions aimed at any funder and potential funding recipient worldwide....
Article
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Protein kinases are critical drug targets for treating a large variety of human diseases. Type-III kinase inhibitors have attracted increasing attention as highly selective therapeutics. Thus, understanding the binding mechanism of existing type-III kinase inhibitors provides useful insights into designing new type-III kinase inhibitors. In this wo...
Article
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p class="Default">Addressing minority health and health disparities has been a missing piece of the puzzle in Big Data science. This article focuses on three priority opportunities that Big Data science may offer to the reduction of health and health care disparities. One opportunity is to incorporate standardized information on demographic and soc...
Article
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The thesis presented here is that biomedical research is based on the trusted exchange of services. That exchange would be conducted more efficiently if the trusted software platforms to exchange those services, if they exist, were more integrated. While simpler and narrower in scope than the services governing biomedical research, comparison to ex...
Article
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Covalently bound protein kinase inhibitors have been frequently designed to target non-catalytic cysteines at the ATP binding site. Thus, it is important to know if a given cysteine can form a covalent bond. Here we combine a function-site interaction fingerprint method and DFT calculations to determine the potential of cysteines to form a covalent...
Article
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The iconic image of the DNA double helix embodies the central role that three-dimensional structures play in understanding biological processes, which, in turn, impact health and well-being. Here, that role is explored through the eyes of one scientist, who has been lucky enough to have over 150 talented people pass through his laboratory. Each con...
Article
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We developed a new software tool, BioJava-ModFinder, for identifying protein modifications observed in 3D structures archived in the Protein Data Bank (PDB). Information on more than 400 types of protein modifications were collected and curated from annotations in PDB, RESID, and PSI-MOD. We divided these modifications into three categories: modifi...
Preprint
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So why make your work available as preprints? There are perceived positives and negatives to disclosing scientific work in the form of a preprint, explored here in the form of 10 Simple Rules. These rules, if they pass review, will appear as part of the PLOS Computational Biology Ten Simple Rules Collection. The rules cover such issues as reward, i...
Preprint
Full-text available
So why make your work available as preprints? There are perceived positives and negatives to disclosing scientific work in the form of a preprint, explored here in the form of 10 Simple Rules. These rules, if they pass review, will appear as part of the PLOS Computational Biology Ten Simple Rules Collection. The rules cover such issues as reward, i...
Article
Full-text available
Background: The success of genome-scale models (GEMs) can be attributed to the high-quality, bottom-up reconstructions of metabolic, protein synthesis, and transcriptional regulatory networks on an organism-specific basis. Such reconstructions are biochemically, genetically, and genomically structured knowledge bases that can be converted into a m...
Article
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Systems pharmacology aims to holistically understand mechanisms of drug actions to support drug discovery and clinical practice. Systems pharmacology modeling (SPM) is data driven. It integrates an exponentially growing amount of data at multiple scales (genetic, molecular, cellular, organismal, and environmental). The goal of SPM is to develop mec...
Preprint
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Systems pharmacology aims to holistically understand genetic, molecular, cellular, organismal, and environmental mechanisms of drug actions through developing mechanistic or predictive models. Data-driven modeling plays a central role in systems pharmacology, and has already enabled biologists to generate novel hypotheses. However, more is needed....
Article
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A preprint is a complete scientific manuscript (often one also being submitted to a peer-reviewed journal) that is uploaded by the authors to a public server without formal review. After a brief inspection to ensure that the work is scientific in nature, the posted scientific manuscript can be viewed without charge on the Web. Thus, preprint server...
Article
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There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders—representing academia, industry, funding agencies, and scholarly publishers—have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent...
Article
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Targeted polypharmacology of kinases has emerged as a promising strategy to design efficient and safe therapeutics. Here, we perform a systematic study of kinase-ligand binding modes for the human structural kinome at scale (208 kinases, 1777 unique ligands, and their complexes) by integrating chemical genomics and structural genomics data and by i...