Dan Jacobson

Dan Jacobson
Oak Ridge National Laboratory | ORNL · Biosciences Division

PhD

About

184
Publications
27,782
Reads
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2,570
Citations
Additional affiliations
February 2009 - December 2014
Stellenbosch University
Position
  • Group Leader, Computational Biology

Publications

Publications (184)
Preprint
CRISPR-Cas9 tools have transformed genetic manipulation capabilities in the laboratory. Empirical rules-of-thumb have been established for only a narrow range of model organisms, and mechanistic underpinnings for sgRNA efficiency remain poorly understood. This work establishes a novel feature set and new public resource, produced with quantum chemi...
Preprint
Despite a global decrease in suicide rates in recent years, death by suicide has increased in the United States. It is therefore imperative to identify the risk factors associated with suicide attempts in order to combat this growing epidemic. In this study, we use an explainable artificial intelligence (X-AI) method, iterative Random Forest (iRF),...
Article
Full-text available
Genome-wide association studies (GWAS) identify genetic variants underlying complex traits but are limited by stringent genome-wide significance thresholds. Here we dramatically relax GWAS stringency by orders of magnitude and apply GRIN (Gene set Refinement through Interacting Networks), which increases confidence in the expanded gene set by retai...
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To identify pan-ancestry and ancestry-specific loci associated with attempting suicide among veterans, we conducted a genome-wide association study (GWAS) of suicide attempts within a large, multi-ancestry cohort of U.S. veterans enrolled in the Million Veterans Program (MVP). Cases were defined as veterans with a documented history of suicide atte...
Preprint
Background Varicose veins represent a common cause of cardiovascular morbidity, with limited available medical therapies. Although varicose veins are heritable and epidemiologic studies have identified several candidate varicose veins risk factors, the molecular and genetic basis remains uncertain. Here, we analyzed the contribution of common genet...
Article
In eukaryotes, fine-scale maps of meiotic recombination events have greatly advanced our understanding of the factors that affect genomic variation patterns and evolution of traits. However, in bacteria that lack natural systems for sexual reproduction, unbiased characterization of recombination landscapes has remained challenging due to variable r...
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Mortality rates during the COVID-19 pandemic have varied by orders of magnitude across communities in the United States. Individual, socioeconomic, and environmental factors have been linked to health outcomes of COVID-19. It is now widely appreciated that the environmental microbiome, composed of microbial communities associated with soil, water,...
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In addition to its essential role in viral polyprotein processing, the SARS-CoV-2 3C-like (3CLpro) protease can cleave human immune signaling proteins, like NF-κB Essential Modulator (NEMO) and deregulate the host immune response. Here, in vitro assays show that SARS-CoV-2 3CLpro cleaves NEMO with fine-tuned efficiency. Analysis of the 2.14 Å resol...
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The heritability of autism spectrum disorder (ASD), based on 680,000 families and five countries, is estimated to be nearly 80%, yet we lack genetic markers that adequately explain it. It is increasingly clear that genomic structural variants (SVs) are a major component of the missing heritability for many complex phenotypes. Here we use a novel me...
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Background Polypharmacy, defined as use of five or more medications concurrently, is associated with adverse health outcomes and people ageing with HIV might be at greater risk than similar uninfected individuals. We aimed to determine whether known pairwise drug interactions (KPDIs) were associated with risk of admission to hospital (hereafter ref...
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The SARS-CoV-2 pandemic recently entered an alarming new phase with the emergence of the variants of concern (VOC) and understanding their biology is paramount to predicting future ones. Current efforts mainly focus on mutations in the spike glycoprotein (S), but changes in other regions of the viral proteome are likely key. We analyzed more than 9...
Article
Hydroxychloroquine (HCQ) was proposed as an early therapy for coronavirus disease 2019 (COVID-19) after in vitro studies indicated possible benefit. Previous in vivo observational studies have presented conflicting results, though recent randomized clinical trials have reported no benefit from HCQ amongst hospitalized COVID-19 patients. We examined...
Preprint
We developed Distilled Graph Attention Policy Networks (DGAPNs), a curiosity-driven reinforcement learning model to generate novel graph-structured chemical representations that optimize user-defined objectives by efficiently navigating a physically constrained domain. The framework is examined on the task of generating molecules that are designed...
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Extensive fibrin deposition in the lungs and altered levels of circulating blood coagulation proteins in COVID-19 patients imply local derangement of pathways that limit fibrin formation and/or promote its clearance. We examined transcriptional profiles of bronchoalveolar lavage fluid (BALF) samples to identify molecular mechanisms underlying these...
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Objective To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States. Design Observational cohort study. Setting Nationwide cohort of patients receiving care in th...
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Image-based symptom scoring of plant diseases is a powerful tool for associating disease resistance with plant genotypes. Advancements in technology have enabled new imaging and image processing strategies for statistical analysis of time-course experiments. There are several tools available for analyzing symptoms on leaves and fruits of crop plant...
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Background A mechanistic understanding of the spread of SARS-CoV-2 and diligent tracking of ongoing mutagenesis are of key importance to plan robust strategies for confining its transmission. Large numbers of available sequences and their dates of transmission provide an unprecedented opportunity to analyze evolutionary adaptation in novel ways. Ad...
Preprint
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Importance Deaths among patients with coronavirus disease 2019 (COVID-19) are partially attributed to venous thromboembolism and arterial thromboses. Anticoagulants prevent thrombosis formation, possess anti-inflammatory and anti-viral properties, and may be particularly effective for treating patients with COVID-19. Objective To evaluate whether...
Article
Radiopharmaceutical Therapy (RPT) continues to demonstrate tremendous potential in improving the therapeutic gains in radiation therapy by specifically delivering radiation to tumors that can be well assessed in terms of dosimetry and imaging. Dosimetry in external beam radiotherapy is standard practice. This is not the case, however, in radiopharm...
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Government retains a non-exclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan...
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Background Available COVID-19 mortality indices are limited to acute inpatient data. Using nationwide medical administrative data available prior to SARS-CoV-2 infection from the US Veterans Health Administration (VA), we developed the VA COVID-19 (VACO) 30-day mortality index and validated the index in two independent, prospective samples. Method...
Article
Identifying similarities and differences in the brain metabolome during different states of consciousness has broad relevance for neuroscience and state-dependent autonomic function. This study focused on prefrontal cortex (PFC) as a brain region known to modulate states of consciousness. Anesthesia was used as a tool to eliminate wakefulness. Unta...
Preprint
Full-text available
In eukaryotes, fine-scale maps of meiotic recombination events have greatly advanced our understanding of the factors that affect genomic variation patterns and evolution of traits. However, in bacteria that lack natural systems for sexual reproduction, unbiased characterization of recombination landscapes has remained challenging due to variable r...
Article
Full-text available
Despite SARS-CoV and SARS-CoV-2 being equipped with highly similar protein arsenals, the corresponding zoonoses have spread among humans at extremely different rates. The specific characteristics of these viruses that led to such distinct outcomes remain unclear. Here, we apply proteome-wide comparative structural analysis aiming to identify the un...
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To understand the genetic mechanisms underlying wood anatomical and morphological traits in Populus trichocarpa, we used 869 unrelated genotypes from a common garden in Clatskanie, Oregon that were previously collected from across the distribution range in western North America. Using GEMMA mixed model analysis, we tested for the association of 25...
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Background Viruses are an underrepresented taxa in the study and identification of microbiome constituents; however, they play an essential role in health, microbiome regulation, and transfer of genetic material. Only a few thousand viruses have been isolated, sequenced, and assigned a taxonomy, which further limits the ability to identify and quan...
Preprint
Full-text available
Background Viruses are underrepresented taxa in the study and identification of microbiome constituents; however, they play an essential role in health, microbiome regulation, and transfer of genetic material. Only a few thousand viruses have been isolated, sequenced, and assigned a taxonomy, which further limits the ability to identify and quantif...
Article
Full-text available
Neither the disease mechanism nor treatments for COVID-19 are currently known. Here, we present a novel molecular mechanism for COVID-19 that provides therapeutic intervention points that can be addressed with existing FDA-approved pharmaceuticals. The entry point for the virus is ACE2, which is a component of the counteracting hypotensive axis of...
Chapter
We demonstrate a selection of network and machine learning techniques useful in the analysis of complex datasets, including 2-way similarity networks, Markov clustering, enrichment statistical networks, FCROS differential analysis, and random forests. We demonstrate each of these techniques on the Populus trichocarpa gene expression atlas.
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Full-text available
Neither the disease mechanism nor treatments for COVID-19 are currently known. Here we present a novel molecular mechanism for COVID-19 that provides therapeutic intervention points that can be addressed with existing FDA-approved pharmaceuticals. The entry point for the virus is ACE2, which is a component of the counteracting hypotensive axis of R...
Article
Full-text available
Neither the disease mechanism nor treatments for COVID-19 are currently known. Here, we present a novel molecular mechanism for COVID-19 that provides therapeutic intervention points that can be addressed with existing FDA-approved pharmaceuticals. The entry point for the virus is ACE2, which is a component of the counteracting hypotensive axis of...
Article
Full-text available
This study quantified eight, small molecule neurotransmitters collected simultaneously from prefrontal cortex of C57BL/6J mouse (n=23) during wakefulness and during isoflurane anesthesia (1.3%). Using isoflurane anesthesia as an independent variable enabled evaluation of the hypothesis that isoflurane anesthesia differentially alters concentrations...
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Using a Systems Biology approach, we integrated genomic, transcriptomic, proteomic, and molecular structure information to provide a holistic understanding of the COVID-19 pandemic. The expression data analysis of the Renin Angiotensin System indicates mild nasal, oral or throat infections are likely and that the gastrointestinal tissues are a comm...
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Background: Potato is the third most consumed crop in the world. Breeding for traits such as yield, product quality and pathogen resistance are main priorities. Identifying molecular signatures of these and other important traits is important in future breeding efforts. In this study, a progeny population from a cross between a breeding line, SW93...
Preprint
Full-text available
Background Potato is the third most consumed crop in the world. Breeding for traits such as yield, product quality and pathogen resistance are main priorities. Identifying molecular signatures of these and other important traits is important in future breeding efforts. In this study, a progeny population from a cross between a breeding line, SW93-1...
Article
Human population growth and accelerated climate change necessitate agricultural improvements using designer crop ideotypes (idealized plants that can grow in niche environments). Diverse and highly skilled research groups must integrate efforts to bridge the gaps needed to achieve international goals toward sustainable agriculture. Given the scale...
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It is becoming increasingly evident that the efficacy of single-gene computational analyses for complex traits is nearly exhausted and future advances hinge on unraveling the intricate combinatorial interactions among multiple genes. However, the discovery of modules of genes working in concert to manifest a complex trait has been crippled by combi...
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Necrotrophic fungi constitute the largest group of plant fungal pathogens that cause heavy crop losses world‐wide. Phymatotrichopsis omnivora is a broad host, soil borne necrotrophic fungal pathogen that infects over 2,000 dicotyledonous plants. The molecular basis of such broad host range is unknown. We conducted cell biology and transcriptomic st...
Preprint
Full-text available
Background Potato is the third most consumed crop in the world. Breeding for traits such as yield, product quality and pathogen resistance are main priorities. Identifying molecular signatures of these and other important traits is important in future breeding efforts. In this study, a progeny population from a cross between a breeding line, SW93-1...
Article
Full-text available
As time progresses and technology improves, biological data sets are continuously increasing in size. New methods and new implementations of existing methods are needed to keep pace with this increase. In this paper, we present a high-performance computing (HPC)-capable implementation of Iterative Random Forest (iRF). This new implementation enable...
Preprint
As time progresses and technology improves, biological data sets are continuously increasing in size. New methods and new implementations of existing methods are needed to keep pace with this increase. In this paper, we present a high performance computing(HPC)-capable implementation of Iterative Random Forest (iRF). This new implementation enables...
Preprint
Full-text available
Background Potato is the third most consumed crop in the world. Breeding for traits such as yield, product quality and pathogen resistance are main priorities. Identifying molecular signatures of these and other important traits is important in future breeding efforts. In this study, a progeny population from a cross between a breeding line, SW93-1...
Article
Full-text available
Populus trichocarpa is an important biofuel feedstock that has been the target of extensive research and is emerging as a model organism for plants, especially woody perennials. This research has generated several large ‘omics datasets. However, only few studies in Populus have attempted to integrate various data types. This review will summarize v...
Article
Paternal cocaine use causes phenotypic alterations in offspring behavior and associated neural processing. In rodents, changes in first generation (F1) offspring include drug reward behavior, circadian timing, and anxiety responses. This study, utilizing a murine (C57BL/6J) oral cocaine model, examines the effects of paternal cocaine exposure on fu...
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Plants serve as host to numerous microorganisms. The members of these microbial communities interact among each other and with the plant, and there is increasing evidence to suggest that the microbial community may promote plant growth, improve drought tolerance, facilitate pathogen defense and even assist in environmental remediation. Therefore, i...
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The molecular mechanisms underlying mycorrhizal symbioses, the most ubiquitous and impactful mutualistic plant–microbial interaction in nature, are largely unknown. Through genetic mapping, resequencing and molecular validation, we demonstrate that a G-type lectin receptor-like kinase (lecRLK) mediates the symbiotic interaction between Populus and...
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Precision medicine and the continuous analysis of “Big data” promises to improve patient outcomes dramatically in the near future. Very recently, healthcare facilities have started to explore automatic collection of patient-specific physiological data with the aim of reducing nursing workload and decreasing manual data entry errors. In addition to...
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In the original version of this article, the incorrect version of Fig. 3 was published. Following is the correct figure.
Article
Breeding crops for high yield and superior adaptability to new and variable climates is imperative to ensure continued food security, biomass production, and ecosystem services. Advances in genomics and phenomics are delivering insights into the complex biological mechanisms that underlie plant functions in response to environmental perturbations....
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Full-text available
Various 'omics data types have been generated for Populus trichocarpa, each providing a layer of information which can be represented as a density signal across a chromosome. We make use of genome sequence data, variants data across a population as well as methylation data across 10 different tissues, combined with wavelet-based signal processing t...
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Various patterns of multi-phenotype associations (MPAs) exist in the results of Genome Wide Association Studies (GWAS) involving different topologies of single nucleotide polymorphism (SNP)-phenotype associations. These can provide interesting information about the different impacts of a gene on closely related phenotypes or disparate phenotypes (p...
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Seeds are involved in the vertical transmission of microorganisms in plants and act as reservoirs for the plant microbiome. They could serve as carriers of pathogens, making the study of microbial interactions on seeds important in the emergence of plant diseases. We studied the influence of biological disturbances caused by seed transmission of tw...
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Serendipitaceae represents a diverse fungal group in the Basidiomycota that includes endophytes and lineages that repeatedly evolved ericoid, orchid, and ectomycorrhizal lifestyle. Plants rely upon both nitrogen and phosphorous, for essential growth processes and are often provided by mycorrhizae. In this study, we investigated the cellular proteom...
Data
Distributions of selected network topology measures for the Experiment 2 operational taxonomic unit (OTU) correlation network.
Data
Primer sequence information for 454 primers used in this study.
Data
Contingency table used in the calculation of Fisher Exact Tests. Each mij is entry ij of an operational taxonomic unit (out) matrix/binned OTU matrix M.
Data
Boxplots showing the relative abundance of fungi and bacteria across different hierarchical classification for the two experiments. (A) Fungi across different soils (Experiment 2: Soil origin); (B) Fungi across different Populus genotypes; (C) Bacteria across different soils (Experiment 2: Soil origin); (D) Bacteria across different Populus genotyp...