Publications by authors named "Overton J"

Background: Symptoms of depression are associated with impaired interoceptive processing of bodily sensation. The antidepressant effects of subcallosal cingulate deep brain stimulation (SCC DBS) include acute change in bodily sensation, and the SCC target is connected to cortical regions critically involved in interoception. This study tests whether cortical interoceptive processing is modulated by SCC DBS for treatment resistant depression (TRD).

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Background: While unstructured data, such as free text, constitutes a large amount of publicly available biomedical data, it is underutilized in automated analyses due to the difficulty of extracting meaning from it. Normalizing free-text data, , removing inessential variance, enables the use of structured vocabularies like ontologies to represent the data and allow for harmonized queries over it. This paper presents an adaptable tool for free-text normalization and an evaluation of the application of this tool to two different sets of unstructured biomedical data curated from the literature in the Immune Epitope Database (IEDB): age and data-location.

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Over the past 20 years, the Immune Epitope Database (IEDB, iedb.org) has established itself as the foremost resource for immune epitope data. The IEDB catalogs published epitopes and their contextual experimental data in a freely searchable public resource.

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Mucormycosis (zygomycosis) is a severe and often fatal mycotic infection affecting primarily immunocompromised individuals. A 61-year-old female with type 2 diabetes mellitus and end-stage renal disease developed septic shock in association with mucormycosis. Despite antifungal treatment with liposomal amphotericin B, the patient's condition rapidly deteriorated, leading to death within 48 hours.

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Whole-genome sequencing (WGS), whole-exome sequencing (WES) and array genotyping with imputation (IMP) are common strategies for assessing genetic variation and its association with medically relevant phenotypes. To date, there has been no systematic empirical assessment of the yield of these approaches when applied to hundreds of thousands of samples to enable the discovery of complex trait genetic signals. Using data for 100 complex traits from 149,195 individuals in the UK Biobank, we systematically compare the relative yield of these strategies in genetic association studies.

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Systems vaccinology studies have been used to build computational models that predict individual vaccine responses and identify the factors contributing to differences in outcome. Comparing such models is challenging due to variability in study designs. To address this, we established a community resource to compare models predicting booster responses and generate experimental data for the explicit purpose of model evaluation.

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Article Synopsis
  • The genetic factors contributing to stroke risk in South Asians remain largely unstudied, with a recent study examining 75,000 Pakistanis using exome-wide sequencing.
  • A specific genetic variant, NOTCH3 p.Arg1231Cys, was found to be more common in South Asians (0.58%) compared to Western Europeans (0.019%) and was significantly linked to hemorrhagic and overall stroke risk.
  • This variant accounts for about 2.0% of hemorrhagic strokes and 1.1% of all strokes in South Asians, emphasizing the importance of including diverse populations in genetic research for better understanding and treatment of stroke.
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Context: Peptidylglycine-α-amidating monooxygenase (PAM) is a critical enzyme in the endocrine system responsible for activation, by amidation, of bioactive peptides.

Objective: To define the clinical phenotype of carriers of genetic mutations associated with impaired PAM-amidating activity (PAM-AMA).

Design: We used genetic and phenotypic data from cohort studies: the Malmö Diet and Cancer (MDC; 1991-1996; reexamination in 2002-2012), the Malmö Preventive Project (MPP; 2002-2006), and the UK Biobank (UKB; 2012).

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Article Synopsis
  • COVID-19 and influenza are respiratory illnesses caused by different viruses but share some symptoms and clinical risk factors, yet their genetic connections remain poorly understood.
  • A study involving over 18,000 influenza cases and nearly 276,000 control subjects found no common genetic risk factors between COVID-19 and influenza, revealing specific gene variants linked only to influenza.
  • The research highlights the potential for targeting cell surface receptors involved in viral entry, showing that manipulating specific genes could lead to treatments that prevent both COVID-19 and influenza infections.
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Dormancy in seeds is a key persistence mechanism for many flowering plants. Physically dormant (PY) seeds have water impermeable seed coats, and in fire-prone systems a common mechanism for dormancy release is fire-induced soil heating. However, the thermal thresholds innate to seeds with PY may be influenced by vegetation, climate, and fire regimes, varying substantially between populations of the same species.

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  • Researchers analyzed genetic data from nearly 1 million individuals to create a comprehensive catalogue of human protein-coding variations, shedding light on gene function and the frequency of rare coding variants.
  • The study identified over 10 million missense and 1.1 million loss-of-function variants, discovering 1,751 novel genes with rare biallelic loss-of-function variants and 3,988 genes intolerant to these variants.
  • They estimate that 3% of people carry a clinically significant genetic variant and provide public access to their data to enhance genetic interpretation and support precision medicine.
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Systems vaccinology studies have identified factors affecting individual vaccine responses, but comparing these findings is challenging due to varying study designs. To address this lack of reproducibility, we established a community resource for comparing Bordetella pertussis booster responses and to host annual contests for predicting patients' vaccination outcomes. We report here on our experiences with the "dry-run" prediction contest.

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Objective: Non-literal expressions such as sarcasm, metaphor and simile refer to words and sentences that convey meanings or intentions that are different and more abstract than literal expressions. Neuroimaging studies have shown activations in a variety of frontal, parietal and temporal brain regions implicated in non-literal language processing. However, neurophysiological correlates of these brain areas underlying non-literal processing remain underexplored.

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Background: A critical advance in depression research is to clarify the hypothesized role of interoceptive processing in neural mechanisms of treatment efficacy. This study tests whether cortical interoceptive processing, as indexed by the heartbeat-evoked potential (HEP), is modulated by deep brain stimulation (DBS) to the subcallosal cingulate (SCC) for treatment resistant depression (TRD).

Methods: Eight patients with TRD were enrolled in a study of SCC DBS safety and efficacy.

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Article Synopsis
  • The Mexico City Prospective Study is a large-scale research initiative involving over 150,000 adults from urban areas in Mexico City, aimed at understanding genetic diversity and ancestry.
  • The study reveals a mix of Indigenous American, European, and African ancestries among participants, highlighting significant genetic differences and a unique genetic landscape within the Indigenous Mexican population.
  • Researchers created a valuable reference panel for genetic research, improving the accuracy of studying genetic variants in populations with high Indigenous ancestry, and providing essential resources for future genetic studies in both Mexico and the US.
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Computational models that predict an individual's response to a vaccine offer the potential for mechanistic insights and personalized vaccination strategies. These models are increasingly derived from systems vaccinology studies that generate immune profiles from human cohorts pre- and post-vaccination. Most of these studies involve relatively small cohorts and profile the response to a single vaccine.

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In this study, we leveraged the combined evidence of rare coding variants and common alleles to identify therapeutic targets for osteoporosis. We undertook a large-scale multiancestry exome-wide association study for estimated bone mineral density, which showed that the burden of rare coding alleles in 19 genes was associated with estimated bone mineral density (P < 3.6 × 10).

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The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease.

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Carotenoids are determinants of reproductive fitness and egg quality. Here we studied the accumulation of astaxanthin (AX), canthaxanthin (CA) zeaxanthin (ZX), lutein (LU), retinol (RX) and dehydroretinol (DR) during vitellogenesis comparing previtellogenic and vitellogenic pikeperch () eggs (n = 5 each), as well as selected tissues (liver, fat and muscles) in first süawning females (1176-1450 g). Futhermore, we compared egg batches with high (88-99% hatching rate, n = 5) or low (40-67% hatching rate, n= 5) egg quality.

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Coding variants that have significant impact on function can provide insights into the biology of a gene but are typically rare in the population. Identifying and ascertaining the frequency of such rare variants requires very large sample sizes. Here, we present the largest catalog of human protein-coding variation to date, derived from exome sequencing of 985,830 individuals of diverse ancestry to serve as a rich resource for studying rare coding variants.

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