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Papers by Nicholas Lewin-koh
Comprehensive R Archive Network (CRAN), Sep 7, 2021
Attached is a copy of the revised manuscript of "Statistical Techniques to Construct Assays for I... more Attached is a copy of the revised manuscript of "Statistical Techniques to Construct Assays for Identifying Likely Responders to a Treatment under Evaluation from Cell Line Genomic Data", formerly entitled "Deriving Clinical Assays from Cell Line Genomic Data" (MS 4241051003512508). We thank the reviewers for in-depth reading and helpful comments on the manuscript. We have made every effort to address all comments completely. Most have of our responses involve amendments to the manuscript which have improved it substantially. HereBelow is find a list of our responses to each of the comments from the two reviewers:. Comments from Ajit Narayanan (Reviewer 1 & 2& 2): We thank Dr. Narayanan for his enthusiasm with regards to the submitted manuscript. A severalMany good points have been broughtraised. up which we hope to address below. While a full account of the impact of pre-processing procedures on prediction models is beyond the scope of this manuscript, it is certainly a worthy and interesting topic and we have endeavored to present and defend our preprocessing approaches more clearly in the manuscript.
Open Forum Infectious Diseases, 2019
Background. Staphylococcus aureus (SA) bacteremia often requires a long treatment duration with a... more Background. Staphylococcus aureus (SA) bacteremia often requires a long treatment duration with antibiotics to prevent relapse due to the ability of SA to establish reservoirs of infection in sites such as heart and bone. These metastatic sites of infection cannot be serially sampled to monitor the clearance of SA infection. This study aimed to establish a link between persistence of circulating SA deoxyribonucleic acid (SA-DNA) and tissue reservoirs in patients with SA bacteremia. Methods. A highly sensitive quantitative polymerase chain reaction was used to measure whole blood SA-DNA and plasma-derived SA cell-free DNA (SA-cfDNA) in a set of longitudinal samples from 73 patients with confirmed SA bacteremia and correlated with clinical features. Results. Blood SA-DNA was detected for longer than the duration of positive blood cultures. Longer duration of circulating bacterial DNA was observed in complicated SA bacteremia infections, such as endocarditis and osteoarticular infections, compared with uncomplicated bloodstream infections. In contrast, traditional blood cultures demonstrated similar time to clearance regardless of foci of infection. Plasma-derived SA-cfDNA showed concordance with blood SA-DNA levels. Baseline levels of SA-DNA were higher in patients presenting with greater clinical severity and complicated bacteremia. Conclusions. Prolonged levels of circulating SA-DNA in patients with complicated tissue reservoirs after clearance of blood cultures observed in this single-center study should be validated in additional cohorts to assess the potential utility for monitoring clearance of infection in patients with SA bacteremia.
Journal of Allergy and Clinical Immunology, 2016
Current Protocols in Protein Science, 2013
Functional protein microarrays offer the capability for high-throughput protein interaction analy... more Functional protein microarrays offer the capability for high-throughput protein interaction analysis and have long promised to be a powerful tool for understanding protein interactions at the proteome scale. Although popular techniques for protein-protein interaction mapping like yeast-two-hybrid and affinity-purification mass spectrometry have performed well for identifying intracellular protein-protein interactions, the study of interactions between extracellular proteins has remained challenging for these methods. Instead, the use of protein microarrays appears to be a robust and efficient method for the identification of interactions among the members of this class of protein. This unit describes methods for extracellular protein microarray production, screening, and analysis. A protocol is described for enhanced detection of low-affinity interactions by generating multivalent complexes using Fc-fusion bait proteins and protein A microbeads, along with a statistical method for hit scoring and identification of nonspecific interactions.
Author Nicholas J. Lewin-Koh and Roger Bivand, contributions by Edzer J. Pebesma, Eric Archer, Ad... more Author Nicholas J. Lewin-Koh and Roger Bivand, contributions by Edzer J. Pebesma, Eric Archer, Adrian Baddeley, Hans-Jö rg Bibiko, Sté phane Dray, David Forrest, Patrick Giraudoux, Duncan Golicher, Virgilio GÃ3mez Rubio, Patrick Hausmann, Thomas Jagger, ...
BMC Cancer, 2010
Background Developing the right drugs for the right patients has become a mantra of drug developm... more Background Developing the right drugs for the right patients has become a mantra of drug development. In practice, it is very difficult to identify subsets of patients who will respond to a drug under evaluation. Most of the time, no single diagnostic will be available, and more complex decision rules will be required to define a sensitive population, using, for instance, mRNA expression, protein expression or DNA copy number. Moreover, diagnostic development will often begin with in-vitro cell-line data and a high-dimensional exploratory platform, only later to be transferred to a diagnostic assay for use with patient samples. In this manuscript, we present a novel approach to developing robust genomic predictors that are not only capable of generalizing from in-vitro to patient, but are also amenable to clinically validated assays such as qRT-PCR. Methods Using our approach, we constructed a predictor of sensitivity to dacetuzumab, an investigational drug for CD40-expressing malig...
Analytical Biochemistry, 2012
Open access under CC BY-NC-ND license. Open access under CC BY-NC-ND license.
This paper presents aspects of the implementation of a bidirectional link between the Geographic ... more This paper presents aspects of the implementation of a bidirectional link between the Geographic Information System (GIS) ArcView 3.0 TM and the interactive dynamic statistical graphics program XGobi. We describe the main functionality of the link, the underlying Remote Procedure Call (RPC) mechanism, and internal data structures, and discuss topics such as security, concurrency, and linked brushing. We think that these topics are of particular interest to software authors intending to link similar software packages, and software users learning about strengths (and weaknesses) of the implementation of our link. Keywords: Cartographic data; Dynamic statistical graphics; Geographic information system; Interprocess communication; Multivariate spatial data; Spatial cumulative distribution function; Spatial statistics; Spatially lagged scatterplot; Variogram--cloud plot. 1 Introduction Geographic Information Systems (GISs) are used extensively for examining spatial data but, traditiona...
Statistical techniques to construct assays for identifying likely responders to a treatment under... more Statistical techniques to construct assays for identifying likely responders to a treatment under evaluation from cell line genomic data
This paper presents aspects of the implementation of a bidirectional link between the Geographic ... more This paper presents aspects of the implementation of a bidirectional link between the Geographic Information System (GIS) ArcView 3.0 and the interactive dynamic statistical graphics program XGobi. We describe the main functionality of the link, the underlying Remote Procedure Call (RPC) mechanism, and internal data structures, and discuss topics such as security, concurrency, and linked brushing. We think that these topics are of particular interest to software authors intending to link similar software packages, and software users learning about strengths (and weaknesses) of the implementation of our link.
Se proporcionan composiciones, kits y metodos para confirmar el pronostico de fibrosis pulmonar i... more Se proporcionan composiciones, kits y metodos para confirmar el pronostico de fibrosis pulmonar idiopatica en pacientes. Asimismo, se proporcionan composiciones, kits y metodos para diagnosticar subtipos de fibrosis pulmonar idiopatica. Tambien se proporcionan metodos para tratar la fibrosis pulmonar idiopatica.
L'invention concerne des compositions, des kits, et des procedes, concus pour etablir un pron... more L'invention concerne des compositions, des kits, et des procedes, concus pour etablir un pronostic de la fibrose pulmonaire idiopathique chez des patients. L'invention concerne egalement des compositions, des kits, et des procedes, permettant de faire le diagnostic des sous-types de fibrose pulmonaire idiopathique. L'invention concerne enfin des procedes concus pour le traitement de la fibrose pulmonaire idiopathique.
Comprehensive R Archive Network (CRAN), Sep 7, 2021
Attached is a copy of the revised manuscript of "Statistical Techniques to Construct Assays for I... more Attached is a copy of the revised manuscript of "Statistical Techniques to Construct Assays for Identifying Likely Responders to a Treatment under Evaluation from Cell Line Genomic Data", formerly entitled "Deriving Clinical Assays from Cell Line Genomic Data" (MS 4241051003512508). We thank the reviewers for in-depth reading and helpful comments on the manuscript. We have made every effort to address all comments completely. Most have of our responses involve amendments to the manuscript which have improved it substantially. HereBelow is find a list of our responses to each of the comments from the two reviewers:. Comments from Ajit Narayanan (Reviewer 1 & 2& 2): We thank Dr. Narayanan for his enthusiasm with regards to the submitted manuscript. A severalMany good points have been broughtraised. up which we hope to address below. While a full account of the impact of pre-processing procedures on prediction models is beyond the scope of this manuscript, it is certainly a worthy and interesting topic and we have endeavored to present and defend our preprocessing approaches more clearly in the manuscript.
Open Forum Infectious Diseases, 2019
Background. Staphylococcus aureus (SA) bacteremia often requires a long treatment duration with a... more Background. Staphylococcus aureus (SA) bacteremia often requires a long treatment duration with antibiotics to prevent relapse due to the ability of SA to establish reservoirs of infection in sites such as heart and bone. These metastatic sites of infection cannot be serially sampled to monitor the clearance of SA infection. This study aimed to establish a link between persistence of circulating SA deoxyribonucleic acid (SA-DNA) and tissue reservoirs in patients with SA bacteremia. Methods. A highly sensitive quantitative polymerase chain reaction was used to measure whole blood SA-DNA and plasma-derived SA cell-free DNA (SA-cfDNA) in a set of longitudinal samples from 73 patients with confirmed SA bacteremia and correlated with clinical features. Results. Blood SA-DNA was detected for longer than the duration of positive blood cultures. Longer duration of circulating bacterial DNA was observed in complicated SA bacteremia infections, such as endocarditis and osteoarticular infections, compared with uncomplicated bloodstream infections. In contrast, traditional blood cultures demonstrated similar time to clearance regardless of foci of infection. Plasma-derived SA-cfDNA showed concordance with blood SA-DNA levels. Baseline levels of SA-DNA were higher in patients presenting with greater clinical severity and complicated bacteremia. Conclusions. Prolonged levels of circulating SA-DNA in patients with complicated tissue reservoirs after clearance of blood cultures observed in this single-center study should be validated in additional cohorts to assess the potential utility for monitoring clearance of infection in patients with SA bacteremia.
Journal of Allergy and Clinical Immunology, 2016
Current Protocols in Protein Science, 2013
Functional protein microarrays offer the capability for high-throughput protein interaction analy... more Functional protein microarrays offer the capability for high-throughput protein interaction analysis and have long promised to be a powerful tool for understanding protein interactions at the proteome scale. Although popular techniques for protein-protein interaction mapping like yeast-two-hybrid and affinity-purification mass spectrometry have performed well for identifying intracellular protein-protein interactions, the study of interactions between extracellular proteins has remained challenging for these methods. Instead, the use of protein microarrays appears to be a robust and efficient method for the identification of interactions among the members of this class of protein. This unit describes methods for extracellular protein microarray production, screening, and analysis. A protocol is described for enhanced detection of low-affinity interactions by generating multivalent complexes using Fc-fusion bait proteins and protein A microbeads, along with a statistical method for hit scoring and identification of nonspecific interactions.
Author Nicholas J. Lewin-Koh and Roger Bivand, contributions by Edzer J. Pebesma, Eric Archer, Ad... more Author Nicholas J. Lewin-Koh and Roger Bivand, contributions by Edzer J. Pebesma, Eric Archer, Adrian Baddeley, Hans-Jö rg Bibiko, Sté phane Dray, David Forrest, Patrick Giraudoux, Duncan Golicher, Virgilio GÃ3mez Rubio, Patrick Hausmann, Thomas Jagger, ...
BMC Cancer, 2010
Background Developing the right drugs for the right patients has become a mantra of drug developm... more Background Developing the right drugs for the right patients has become a mantra of drug development. In practice, it is very difficult to identify subsets of patients who will respond to a drug under evaluation. Most of the time, no single diagnostic will be available, and more complex decision rules will be required to define a sensitive population, using, for instance, mRNA expression, protein expression or DNA copy number. Moreover, diagnostic development will often begin with in-vitro cell-line data and a high-dimensional exploratory platform, only later to be transferred to a diagnostic assay for use with patient samples. In this manuscript, we present a novel approach to developing robust genomic predictors that are not only capable of generalizing from in-vitro to patient, but are also amenable to clinically validated assays such as qRT-PCR. Methods Using our approach, we constructed a predictor of sensitivity to dacetuzumab, an investigational drug for CD40-expressing malig...
Analytical Biochemistry, 2012
Open access under CC BY-NC-ND license. Open access under CC BY-NC-ND license.
This paper presents aspects of the implementation of a bidirectional link between the Geographic ... more This paper presents aspects of the implementation of a bidirectional link between the Geographic Information System (GIS) ArcView 3.0 TM and the interactive dynamic statistical graphics program XGobi. We describe the main functionality of the link, the underlying Remote Procedure Call (RPC) mechanism, and internal data structures, and discuss topics such as security, concurrency, and linked brushing. We think that these topics are of particular interest to software authors intending to link similar software packages, and software users learning about strengths (and weaknesses) of the implementation of our link. Keywords: Cartographic data; Dynamic statistical graphics; Geographic information system; Interprocess communication; Multivariate spatial data; Spatial cumulative distribution function; Spatial statistics; Spatially lagged scatterplot; Variogram--cloud plot. 1 Introduction Geographic Information Systems (GISs) are used extensively for examining spatial data but, traditiona...
Statistical techniques to construct assays for identifying likely responders to a treatment under... more Statistical techniques to construct assays for identifying likely responders to a treatment under evaluation from cell line genomic data
This paper presents aspects of the implementation of a bidirectional link between the Geographic ... more This paper presents aspects of the implementation of a bidirectional link between the Geographic Information System (GIS) ArcView 3.0 and the interactive dynamic statistical graphics program XGobi. We describe the main functionality of the link, the underlying Remote Procedure Call (RPC) mechanism, and internal data structures, and discuss topics such as security, concurrency, and linked brushing. We think that these topics are of particular interest to software authors intending to link similar software packages, and software users learning about strengths (and weaknesses) of the implementation of our link.
Se proporcionan composiciones, kits y metodos para confirmar el pronostico de fibrosis pulmonar i... more Se proporcionan composiciones, kits y metodos para confirmar el pronostico de fibrosis pulmonar idiopatica en pacientes. Asimismo, se proporcionan composiciones, kits y metodos para diagnosticar subtipos de fibrosis pulmonar idiopatica. Tambien se proporcionan metodos para tratar la fibrosis pulmonar idiopatica.
L'invention concerne des compositions, des kits, et des procedes, concus pour etablir un pron... more L'invention concerne des compositions, des kits, et des procedes, concus pour etablir un pronostic de la fibrose pulmonaire idiopathique chez des patients. L'invention concerne egalement des compositions, des kits, et des procedes, permettant de faire le diagnostic des sous-types de fibrose pulmonaire idiopathique. L'invention concerne enfin des procedes concus pour le traitement de la fibrose pulmonaire idiopathique.