Scholars@Duke
Steven B. Haase

Steven B. Haase

Professor of Biology
Biology
steve.haase@duke.edu
Box 90338, Durham, NC 27708-1000
4316 French, Durham, NC 27708

Selected Publications

AutoGater: a weakly supervised neural network model to gate cells in flow cytometric analyses.

Journal Article Scientific reports · October 2024 Flow cytometry is a useful and efficient method for the rapid characterization of a cell population based on the optical and fluorescence properties of individual cells. Ideally, the cell population would consist of only healthy viable cells as dead cells ... Full text Cite

A yeast cell cycle pulse generator model shows consistency with multiple oscillatory and checkpoint mutant datasets.

Journal Article Mathematical biosciences · January 2024 Modeling biological systems holds great promise for speeding up the rate of discovery in systems biology by predicting experimental outcomes and suggesting targeted interventions. However, this process is dogged by an identifiability issue, in which networ ... Full text Cite

The parasite intraerythrocytic cycle and human circadian cycle are coupled during malaria infection.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · June 2023 During infections with the malaria parasites Plasmodium vivax, patients exhibit rhythmic fevers every 48 h. These fever cycles correspond with the time the parasites take to traverse the intraerythrocytic cycle (IEC). In other Plasmodium spec ... Full text Cite

Alignment of Synchronized Time-Series Data Using the Characterizing Loss of Cell Cycle Synchrony Model for Cross-Experiment Comparisons.

Journal Article Journal of visualized experiments : JoVE · June 2023 Investigating the cell cycle often depends on synchronizing cell populations to measure various parameters in a time series as the cells traverse the cell cycle. However, even under similar conditions, replicate experiments display differences in the time ... Full text Cite

Learning perturbation-inducible cell states from observability analysis of transcriptome dynamics.

Journal Article Nature communications · May 2023 A major challenge in biotechnology and biomanufacturing is the identification of a set of biomarkers for perturbations and metabolites of interest. Here, we develop a data-driven, transcriptome-wide approach to rank perturbation-inducible genes from time-s ... Full text Cite

Collaborative methods to enhance reproducibility and accelerate discovery

Journal Article Digital Discovery · February 1, 2023 Many domains across physical, life, and social sciences suffer from incomplete models of constructs (e.g., organisms, environments, behaviors), which hinders reproducibility and the pace of discovery. Critically, the prevailing research paradigm, of indivi ... Full text Cite

Robustness and reproducibility of simple and complex synthetic logic circuit designs using a DBTL loop.

Journal Article Synthetic biology (Oxford, England) · January 2023 Computational tools addressing various components of design-build-test-learn (DBTL) loops for the construction of synthetic genetic networks exist but do not generally cover the entire DBTL loop. This manuscript introduces an end-to-end sequence of tools t ... Full text Cite

Experimental guidance for discovering genetic networks through hypothesis reduction on time series.

Journal Article PLoS computational biology · October 2022 Large programs of dynamic gene expression, like cell cyles and circadian rhythms, are controlled by a relatively small "core" network of transcription factors and post-translational modifiers, working in concerted mutual regulation. Recent work suggests th ... Full text Cite

Predictive values of time-dense SARS-CoV-2 wastewater analysis in university campus buildings.

Journal Article The Science of the total environment · August 2022 Wastewater-based SARS-CoV-2 surveillance on college campuses has the ability to detect individual clinical COVID-19 cases at the building-level. High concordance of wastewater results and clinical cases has been observed when calculated over a time window ... Full text Cite

Conservation of dynamic characteristics of transcriptional regulatory elements in periodic biological processes.

Journal Article BMC bioinformatics · March 2022 BackgroundCell and circadian cycles control a large fraction of cell and organismal physiology by regulating large periodic transcriptional programs that encompass anywhere from 15 to 80% of the genome despite performing distinct functions. In eac ... Full text Cite

Round Trip: An Automated Pipeline for Experimental Design, Execution, and Analysis.

Journal Article ACS synthetic biology · February 2022 Synthetic biology is a complex discipline that involves creating detailed, purpose-built designs from genetic parts. This process is often phrased as a Design-Build-Test-Learn loop, where iterative design improvements can be made, implemented, measured, an ... Full text Cite

Association of COVID-19 Quarantine Duration and Postquarantine Transmission Risk in 4 University Cohorts.

Journal Article JAMA network open · February 2022 ImportanceOptimal quarantine length for COVID-19 infection is unclear, in part owing to limited empirical data.ObjectiveTo assess postquarantine transmission risk for various quarantine lengths and potential associations between quarantin ... Full text Cite

Highly-automated, high-throughput replication of yeast-based logic circuit design assessments.

Journal Article Synthetic biology (Oxford, England) · January 2022 We describe an experimental campaign that replicated the performance assessment of logic gates engineered into cells of Saccharomyces cerevisiae by Gander et al. Our experimental campaign used a novel high-throughput experimentation framework ... Full text Cite

Improved datasets and evaluation methods for the automatic prediction of DNA-binding proteins.

Journal Article Bioinformatics (Oxford, England) · December 2021 MotivationAccurate automatic annotation of protein function relies on both innovative models and robust datasets. Due to their importance in biological processes, the identification of DNA-binding proteins directly from protein sequence has been t ... Full text Cite

Inherent Dynamics Visualizer, an Interactive Application for Evaluating and Visualizing Outputs from a Gene Regulatory Network Inference Pipeline.

Journal Article Journal of visualized experiments : JoVE · December 2021 Developing gene regulatory network models is a major challenge in systems biology. Several computational tools and pipelines have been developed to tackle this challenge, including the newly developed Inherent Dynamics Pipeline. The Inherent Dynamics Pipel ... Full text Cite

Impact of Sickle Cell Trait Hemoglobin on the Intraerythrocytic Transcriptional Program of Plasmodium falciparum.

Journal Article mSphere · October 27, 2021 Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening falciparum malaria in African children. Despite this clear protection, the molecular mechanisms by which HbAS confers these protective phenotypes remain incompl ... Full text Link to item Cite

Assessment of Simulated Surveillance Testing and Quarantine in a SARS-CoV-2-Vaccinated Population of Students on a University Campus.

Journal Article JAMA Health Forum · October 2021 IMPORTANCE: The importance of surveillance testing and quarantine on university campuses to limit SARS-CoV-2 transmission needs to be reevaluated in the context of a complex and rapidly changing environment that includes vaccines, variants, and waning immu ... Full text Open Access Link to item Cite

Inference of Gene Regulatory Network Uncovers the Linkage between Circadian Clock and Crassulacean Acid Metabolism in Kalanchoë fedtschenkoi.

Journal Article Cells · August 2021 The circadian clock drives time-specific gene expression, enabling biological processes to be temporally controlled. Plants that conduct crassulacean acid metabolism (CAM) photosynthesis represent an interesting case of circadian regulation of gene express ... Full text Cite

Implementation of a Pooled Surveillance Testing Program for Asymptomatic SARS-CoV-2 Infections on a College Campus - Duke University, Durham, North Carolina, August 2-October 11, 2020.

Journal Article MMWR Morb Mortal Wkly Rep · November 20, 2020 On university campuses and in similar congregate environments, surveillance testing of asymptomatic persons is a critical strategy (1,2) for preventing transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). All students at D ... Full text Open Access Link to item Cite

An intrinsic oscillator drives the blood stage cycle of the malaria parasite Plasmodium falciparum.

Journal Article Science (New York, N.Y.) · May 2020 The blood stage of the infection of the malaria parasite Plasmodium falciparum exhibits a 48-hour developmental cycle that culminates in the synchronous release of parasites from red blood cells, which triggers 48-hour fever cycles in the host. This ... Full text Cite

Using extremal events to characterize noisy time series.

Journal Article Journal of mathematical biology · April 2020 Experimental time series provide an informative window into the underlying dynamical system, and the timing of the extrema of a time series (or its derivative) contains information about its structure. However, the time series often contain significant mea ... Full text Cite

Conservation of dynamic characteristics of transcriptional regulatory elements in periodic biological processes

Journal Article · 2020 Cell and circadian cycles control a large fraction of cell and organismal physiology by regulating large periodic transcriptional programs that encompass anywhere from 15-80% of the genome. The gene-regulatory networks (GRNs) controlling these programs wer ... Full text Cite

The cell-cycle transcriptional network generates and transmits a pulse of transcription once each cell cycle.

Journal Article Cell cycle (Georgetown, Tex.) · February 2019 Multiple studies have suggested the critical roles of cyclin-dependent kinases (CDKs) as well as a transcription factor (TF) network in generating the robust cell-cycle transcriptional program. However, the precise mechanisms by which these components func ... Full text Cite

Selecting and assessing challenge problems

Journal Article Theoretical Issues in Ergonomics Science · January 2, 2019 Full text Cite

Layers of regulation of cell-cycle gene expression in the budding yeast Saccharomyces cerevisiae.

Journal Article Mol Biol Cell · November 1, 2018 In the budding yeast Saccharomyces cerevisiae, transcription factors (TFs) regulate the periodic expression of many genes during the cell cycle, including gene products required for progression through cell-cycle events. Experimental evidence coupled with ... Full text Link to item Cite

Conservation and Diversification of Circadian Rhythmicity Between a Model Crassulacean Acid Metabolism Plant Kalanchoë fedtschenkoi and a Model C3 Photosynthesis Plant Arabidopsis thaliana.

Journal Article Frontiers in plant science · January 2018 Crassulacean acid metabolism (CAM) improves photosynthetic efficiency under limited water availability relative to C3 photosynthesis. It is widely accepted that CAM plants have evolved from C3 plants and it is hypothesized that CAM is ... Full text Cite

Connecting virulence pathways to cell-cycle progression in the fungal pathogen Cryptococcus neoformans.

Journal Article Current genetics · October 2017 Proliferation and host evasion are critical processes to understand at a basic biological level for improving infectious disease treatment options. The human fungal pathogen Cryptococcus neoformans causes fungal meningitis in immunocompromised individuals ... Full text Cite

Reconciling conflicting models for global control of cell-cycle transcription.

Journal Article Cell cycle (Georgetown, Tex.) · October 2017 Models for the control of global cell-cycle transcription have advanced from a CDK-APC/C oscillator, a transcription factor (TF) network, to coupled CDK-APC/C and TF networks. Nonetheless, current models were challenged by a recent study that concluded tha ... Full text Cite

Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans.

Journal Article PLoS genetics · December 2016 The pathogenic yeast Cryptococcus neoformans causes fungal meningitis in immune-compromised patients. Cell proliferation in the budding yeast form is required for C. neoformans to infect human hosts, and virulence factors such as capsule formation and mela ... Full text Cite

The Local Edge Machine: inference of dynamic models of gene regulation.

Journal Article Genome biology · October 2016 We present a novel approach, the Local Edge Machine, for the inference of regulatory interactions directly from time-series gene expression data. We demonstrate its performance, robustness, and scalability on in silico datasets with varying behaviors, size ... Full text Cite

SW1PerS: Sliding windows and 1-persistence scoring; discovering periodicity in gene expression time series data.

Journal Article BMC bioinformatics · August 2015 BackgroundIdentifying periodically expressed genes across different processes (e.g. the cell and metabolic cycles, circadian rhythms, etc) is a central problem in computational biology. Biological time series may contain (multiple) unknown signal ... Full text Cite

Checkpoints couple transcription network oscillator dynamics to cell-cycle progression.

Journal Article Genome biology · September 2014 BackgroundThe coupling of cyclin dependent kinases (CDKs) to an intrinsically oscillating network of transcription factors has been proposed to control progression through the cell cycle in budding yeast, Saccharomyces cerevisiae. The transcriptio ... Full text Cite

Topology and control of the cell-cycle-regulated transcriptional circuitry.

Journal Article Genetics · January 2014 Nearly 20% of the budding yeast genome is transcribed periodically during the cell division cycle. The precise temporal execution of this large transcriptional program is controlled by a large interacting network of transcriptional regulators, kinases, and ... Full text Cite

Cell cycle-regulated transcription: effectively using a genomics toolbox.

Journal Article Methods in molecular biology (Clifton, N.J.) · January 2014 The cell cycle comprises a series of temporally ordered events that occur sequentially, including DNA replication, centrosome duplication, mitosis, and cytokinesis. What are the regulatory mechanisms that ensure proper timing and coordination of events dur ... Full text Cite

Analyzing transcription dynamics during the budding yeast cell cycle.

Journal Article Methods in molecular biology (Clifton, N.J.) · January 2014 Assaying global cell cycle-regulated transcription in budding yeast involves extracting RNA from a synchronous population and proper normalization of detected transcript levels. Here, we describe synchronization of Saccharomyces cerevisiae cell populations ... Full text Cite

Analyzing transcription dynamics during the budding yeast cell cycle

Journal Article Methods in Molecular Biology · 2014 Assaying global cell cycle-regulated transcription in budding yeast involves extracting RNA from a synchronous population and proper normalization of detected transcript levels. Here, we describe synchronization of Saccharomyces cerevisiae cell populations ... Full text Cite

Cell cycle-regulated transcription: Effectively using a genomics toolbox

Book · 2014 The cell cycle comprises a series of temporally ordered events that occur sequentially, including DNA replication, centrosome duplication, mitosis, and cytokinesis. What are the regulatory mechanisms that ensure proper timing and coordination of events dur ... Full text Cite

Cell cycle-regulated transcription: Effectively using a genomics toolbox

Book · January 1, 2014 The cell cycle comprises a series of temporally ordered events that occur sequentially, including DNA replication, centrosome duplication, mitosis, and cytokinesis. What are the regulatory mechanisms that ensure proper timing and coordination of events dur ... Full text Cite

Analyzing transcription dynamics during the budding yeast cell cycle

Journal Article Methods in Molecular Biology · January 1, 2014 Assaying global cell cycle-regulated transcription in budding yeast involves extracting RNA from a synchronous population and proper normalization of detected transcript levels. Here, we describe synchronization of Saccharomyces cerevisiae cell populations ... Full text Cite

Branching process deconvolution algorithm reveals a detailed cell-cycle transcription program.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · March 2013 Due to cell-to-cell variability and asymmetric cell division, cells in a synchronized population lose synchrony over time. As a result, time-series measurements from synchronized cell populations do not reflect the underlying dynamics of cell-cycle process ... Full text Cite

New and Redesigned pRS Plasmid Shuttle Vectors for Genetic Manipulation of Saccharomycescerevisiae.

Journal Article G3 (Bethesda, Md.) · May 2012 We have constructed a set of 42 plasmid shuttle vectors based on the widely used pRS series for use in the budding yeast Saccharomyces cerevisiae and the bacterium Escherichia coli. This set of pRSII plasmids includes new shuttle vectors that can be used w ... Full text Cite

Parametric modeling of cellular state transitions as measured with flow cytometry.

Journal Article BMC bioinformatics · April 2012 BackgroundGradual or sudden transitions among different states as exhibited by cell populations in a biological sample under particular conditions or stimuli can be detected and profiled by flow cytometric time course data. Often such temporal pro ... Full text Cite

Close Encounters of the Collaborative Kind

Journal Article Computer · March 2012 Full text Cite

Cyclin-dependent kinases are regulators and effectors of oscillations driven by a transcription factor network.

Journal Article Molecular cell · March 2012 During embryonic cell cycles, B-cyclin-CDKs function as the core component of an autonomous oscillator. Current models for the cell-cycle oscillator in nonembryonic cells are slightly more complex, incorporating multiple G1, S phase, and mitotic cyclin-CDK ... Full text Cite

Design and Analysis of Large-Scale Biological Rhythm Studies: A Comparison of Algorithms for Detecting Periodic Signals in Biological Data

Journal Article PLOS Computational Biology · 2012 The results of a major year-long DARPA funded project to study the performance of a large collection of algorithms for finding periodic gene expression. ... Cite

Parametric modeling of cellular state transitions as measured with flow cytometry.

Journal Article BMC bioinformatics · January 1, 2012 Gradual or sudden transitions among different states as exhibited by cell populations in a biological sample under particular conditions or stimuli can be detected and profiled by flow cytometric time course data. Often such temporal profiles contain featu ... Full text Cite

A generalized model for multi-marker analysis of cell cycle progression in synchrony experiments.

Journal Article Bioinformatics (Oxford, England) · July 2011 MotivationTo advance understanding of eukaryotic cell division, it is important to observe the process precisely. To this end, researchers monitor changes in dividing cells as they traverse the cell cycle, with the presence or absence of morpholog ... Full text Cite

B-cyclin/CDKs regulate mitotic spindle assembly by phosphorylating kinesins-5 in budding yeast.

Journal Article PLoS genetics · May 2010 Although it has been known for many years that B-cyclin/CDK complexes regulate the assembly of the mitotic spindle and entry into mitosis, the full complement of relevant CDK targets has not been identified. It has previously been shown in a variety of mod ... Full text Open Access Cite

Cohesin: it's not just for chromosomes anymore.

Journal Article Cell cycle (Georgetown, Tex.) · May 2010 Full text Cite

B-Cyclin/CDKs regulate mitotic spindle assembly by phosphorylating kinesins-5 in budding yeast

Journal Article PLoS Genetics · May 1, 2010 Although it has been known for many years that B-cyclin/CDK complexes regulate the assembly of the mitotic spindle and entry into mitosis, the full complement of relevant CDK targets has not been identified. It has previously been shown in a variety of mod ... Full text Cite

A branching process model for flow cytometry and budding index measurements in cell synchrony experiments.

Journal Article The annals of applied statistics · January 2009 We present a flexible branching process model for cell population dynamics in synchrony/time-series experiments used to study important cellular processes. Its formulation is constructive, based on an accounting of the unique cohorts in the population as t ... Full text Open Access Cite

Transcription networks and cyclin/CDKs: the yin and yang of cell cycle oscillators.

Journal Article Cell cycle (Georgetown, Tex.) · September 2008 It is widely accepted that the central cell cycle oscillator is based on cyclin/CDK complexes. In a recent study, we challenged this model, and showed that a transcription factor network can drive correctly-timed periodic events independent of cyclin/CDK f ... Full text Cite

Intrinsic and cyclin-dependent kinase-dependent control of spindle pole body duplication in budding yeast.

Journal Article Molecular biology of the cell · August 2008 Centrosome duplication must be tightly controlled so that duplication occurs only once each cell cycle. Accumulation of multiple centrosomes can result in the assembly of a multipolar spindle and lead to chromosome mis-segregation and genomic instability. ... Full text Cite

Global control of cell-cycle transcription by coupled CDK and network oscillators.

Journal Article Nature · June 2008 A significant fraction of the Saccharomyces cerevisiae genome is transcribed periodically during the cell division cycle, indicating that properly timed gene expression is important for regulating cell-cycle events. Genomic analyses of the localization and ... Full text Cite

Microtubule organization: cell shape is destiny.

Journal Article Curr Biol · April 3, 2007 A simple self-assembly pathway generates cytoplasmic microtubule bundles that can locate the cell center and guide spindle assembly in fission yeast. The cylindrical cell shape automatically corrects spindle orientation errors, rendering a checkpoint unnec ... Full text Link to item Cite

A probabilistic model for cell cycle distributions in synchrony experiments.

Journal Article Cell cycle (Georgetown, Tex.) · February 2007 Synchronized populations of cells are often used to study dynamic processes during the cell division cycle. However, the analysis of time series measurements made on synchronized populations is confounded by the fact that populations lose synchrony over ti ... Full text Cite

Distinct mechanisms control the stability of the related S-phase cyclins Clb5 and Clb6.

Journal Article Molecular and cellular biology · March 2006 The yeast S-phase cyclins Clb5 and Clb6 are closely related proteins that are synthesized late in G1. Although often grouped together with respect to function, Clb5 and Clb6 exhibit differences in their ability to promote S-phase progression. DNA replicati ... Full text Cite

Cell cycle analysis of budding yeast using SYTOX Green.

Journal Article Current protocols in cytometry · November 2004 Flow cytometric determination of DNA content is a standard tool for cell cycle analysis in the budding yeast, Saccharomyces cerevisiae. Using SYTOX Green instead of propidium iodide (PI) in a standard ethanol fixation protocol increases the accuracy and re ... Full text Cite

Improved flow cytometric analysis of the budding yeast cell cycle.

Journal Article Cell cycle (Georgetown, Tex.) · March 2002 The budding yeast, Saccharomyces cerevisiae has been a remarkably useful model system for the study of eukaryotic cell cycle regulation. Flow cytometric analysis of DNA content in budding yeast has become a standard tool for the analysis of cell cycle prog ... Cite

A festival of cell-cycle controls.

Journal Article Trends in cell biology · November 2001 The second biennial Salk Cell Cycle meeting convened on 22 June 2001 in San Diego, California. Organized by Tony Hunter and Susan Forsburg of the Salk Institute, the five-day conference was highlighted by enlightening science and plenty of San Diego sunshi ... Full text Cite

Multi-step control of spindle pole body duplication by cyclin-dependent kinase

Journal Article Nature Cell Biology · 2001 Organelles called centrosomes in metazoans or spindle pole bodies (SPBs) in yeast direct the assembly of a bipolar spindle that is essential for faithful segregation of chromosomes during mitosis. Abnormal accumulation of multiple centrosomes leads to g ... Cite

Multi-step control of spindle pole body duplication by cyclin-dependent kinase.

Journal Article Nature cell biology · January 2001 Organelles called centrosomes in metazoans or spindle pole bodies (SPBs) in yeast direct the assembly of a bipolar spindle that is essential for faithful segregation of chromosomes during mitosis. Abnormal accumulation of multiple centrosomes leads to geno ... Full text Cite

Functions of fission yeast orp2 in DNA replication and checkpoint control.

Journal Article Genetics · February 2000 orp2 is an essential gene of the fission yeast Schizosaccharomyces pombe with 22% identity to budding yeast ORC2. We isolated temperature-sensitive alleles of orp2 using a novel plasmid shuffle based on selection against thymidine kinase. Cells bearing the ... Full text Cite

Evidence that a free-running oscillator drives G1 events in the budding yeast cell cycle.

Journal Article Nature · September 1999 In yeast and somatic cells, mechanisms ensure cell-cycle events are initiated only when preceding events have been completed. In contrast, interruption of specific cell-cycle processes in early embryonic cells of many organisms does not affect the timing o ... Full text Cite

Transcription inhibits the replication of autonomously replicating plasmids in human cells.

Journal Article Molecular and cellular biology · April 1994 This study addresses the effect of transcription on replication, using a system based on autonomously replicating plasmids in human cells. We added transcriptional elements from the human cytomegalovirus promoter/enhancer and the human beta-actin promoter ... Full text Cite

Replication control of autonomously replicating human sequences.

Journal Article Nucleic acids research · September 1991 Three autonomously replicating plasmids carrying human genomic DNA and a vector derived from Epstein-Barr virus were studied by density labelling to determine the number of times per cell cycle these plasmids replicate in human cells. Each of the plasmids ... Full text Cite

Isolation of human sequences that replicate autonomously in human cells.

Journal Article Molecular and cellular biology · March 1989 We have isolated a heterogeneous collection of human genomic sequences which replicate autonomously when introduced into human cells. The novel strategy for the isolation of these sequences involved cloning random human DNA fragments into a defective Epste ... Full text Cite

Improved EBV shuttle vectors.

Journal Article Mutation research · March 1989 Shuttle vectors based on Epstein-Barr virus (EBV) replicate autonomously in the nuclei of human cells. These vectors represent reasonable models for chromosomes, have low background mutation frequencies, and have been useful for studying induced mutation i ... Full text Cite