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MiDAS-Meaningful Immunogenetic Data at Scale.

ABSTRACT: Human immunogenetic variation in the form of HLA and KIR types has been shown to be strongly associated with a multitude of immune-related phenotypes. However, association studies involving immunogenetic loci most commonly involve simple analyses of classical HLA allelic diversity, resulting in limitations regarding the interpretability and reproducibility of results. We here present MiDAS, a comprehensive R package for immunogenetic data transformation and statistical analysis. MiDAS recodes input data in the form of HLA alleles and KIR types into biologically meaningful variables, allowing HLA amino acid fine mapping, analyses of HLA evolutionary divergence as well as experimentally validated HLA-KIR interactions. Further, MiDAS enables comprehensive statistical association analysis workflows with phenotypes of diverse measurement scales. MiDAS thus closes the gap between the inference of immunogenetic variation and its efficient utilization to make relevant discoveries related to immune and disease biology. It is freely available under a MIT license.

SUBMITTER: Migdal M

PROVIDER: S-EPMC8284797 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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MiDAS-Meaningful Immunogenetic Data at Scale.

Migdal Maciej M Ruan Dan Fu DF Forrest William F WF Horowitz Amir A Hammer Christian C

PLoS computational biology 20210706 7

Human immunogenetic variation in the form of HLA and KIR types has been shown to be strongly associated with a multitude of immune-related phenotypes. However, association studies involving immunogenetic loci most commonly involve simple analyses of classical HLA allelic diversity, resulting in limitations regarding the interpretability and reproducibility of results. We here present MiDAS, a comprehensive R package for immunogenetic data transformation and statistical analysis. MiDAS recodes in ...[more]

PMID: 34228721

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Project description:BackgroundMajor depressive disorder (MDD) directly impacts patients' lives including symptoms, functioning and health-related quality-of-life (HRQoL). Patient-reported outcomes can capture these impacts, however interpretation of clinical meaningfulness of these measurements are often not readily available. Meaningful change thresholds (MCTs) can be derived for clinical outcome assessments to quantify the change in symptoms that is meaningful to the patient following pharmacologic treatment or other interventions. The objective of this analysis was to determine the within-patient MCT of the self-reported Quality-of-Life in Depression Scale (QLDS) among patients with MDD and active suicidal ideation with intent (MDSI) using an anchor-based approach.MethodsData from 2 randomized phase-3 trials of esketamine nasal spray (ASPIRE I and ASPIRE II) were analyzed. The Montgomery-Åsberg Depression Rating Scale (MADRS) was the primary anchor with three different severity criteria. Other anchor variables utilized were Clinical Global Impression of Severity of Suicidality-revised version, Clinical Global Impression of Imminent Suicide Risk, and EuroQol Visual Analog Scale [EQ-VAS]. Spearman correlation coefficients between the change in QLDS and anchor variables were calculated. The mean change in QLDS score at Day 25 from baseline was calculated based on the categorical change in the anchor. Coefficient yield from linear regression of the mean changes in EQ-VAS and QLDS, and distribution-based approach with ½ SD of change in QLDS were considered.ResultsIn ASPIRE I, mean (SD) improvement in QLDS score among patients with one category improvement in MADRS from baseline to Day 25 was - 8.22 (8.87), - 8.30 (9.01), and - 8.20 (8.92) using severity criteria #1, #2, and #3, respectively. Patients who achieved a 7-point improvement (MCT) in EQ-VAS yielded a mean - 9.69-point improvement in QLDS at Day 25. The ½ SD of change in QLDS was 5.63. Similar results were obtained for ASPIRE II. The MCTs identified using multiple anchors across both trials ranged from - 11.4 to - 6.7 and had an overall mean of - 7.90 (ASPIRE I) and - 7.92 (ASPIRE II). Thus, an 8-point change was recommended as the MCT for QLDS.ConclusionThe recommended MCT will help quantify within-person changes in HRQoL using patient-reported QLDS and determine meaningful treatment benefit in an MDD patient population with acute suicidal ideation or behavior.Trial registrationName of the registry: ClinicalTrials.gov.Trial registration numberASPIRE I (NCT03039192), ASPIRE II (NCT03097133). Date of registration: February 01, 2017; March 31, 2017. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03039192 ; https://clinicaltrials.gov/ct2/show/NCT03097133 .

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MiDAS-Meaningful Immunogenetic Data at Scale.

Publications

MiDAS-Meaningful Immunogenetic Data at Scale.

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