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Article ; Online: Differential Methylation of Chronic Obstructive Pulmonary Disease Lung Macrophage Genes Sheds Light on Disease Pathogenesis.

Konigsberg, Iain R / Yang, Ivana V

American journal of respiratory cell and molecular biology

2022 Volume 66, Issue 6, Page(s) 589–590

MeSH term(s)	Epigenome ; Humans ; Lung/physiopathology ; Macrophages ; Methylation ; Pulmonary Disease, Chronic Obstructive/physiopathology
Language	English
Publishing date	2022-04-04
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1025960-0
ISSN	1535-4989 ; 1044-1549
ISSN (online)	1535-4989
ISSN	1044-1549
DOI	10.1165/rcmb.2022-0125ED
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Article ; Online: It's in the (Epi)genetics: Effects of DNA Methylation on Gene Expression in Atopic Asthma?

Konigsberg, Iain R / Yang, Ivana V

Chest

2020 Volume 158, Issue 5, Page(s) 1799–1801

MeSH term(s)	Asthma/genetics ; DNA Methylation ; Gene Expression ; Humans ; Phenotype
Language	English
Publishing date	2020-10-22
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1016/j.chest.2020.07.050
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Article ; Online: TestDimorph: An R package for analysis of interpopulation sexual dimorphism differences using summary statistics.

Abulnoor, Bassam A / Attia, MennattAllah Hassan / Konigsberg, Iain R / Konigsberg, Lyle W

American journal of biological anthropology

2023 Volume 182, Issue 3, Page(s) 487–498

Abstract: ... the first R package dedicated to testing and comparing the degree of sexual dimorphism among different ...

Abstract	Objective: The degree of sexual dimorphism in certain traits between males and females differ from one sample to another. Although trait differences by sex are often reported in bioanthropological research, few studies test for statistical significance or make raw data available. TestDimorph is the first R package dedicated to testing and comparing the degree of sexual dimorphism among different samples by leveraging summary statistics. Materials and methods: We provide two approaches of analysis of inter-sample differences in degree of sexual dimorphism: univariate and multivariate for two or more samples. The methods follow upon publications primarily from the AJBA. Within-sex size variability between samples is compared using one-way ANOVA followed by control for multiple pairwise comparisons. In addition, we compute the overlapping area between the density functions of two normal distributions from the mixture intersection index or the non-overlapping area using the dissimilarity index as well as Hedges' g with inferential support using the 95% confidence interval. Finally, we use a multivariate analysis of differences in patterning of sexual dimorphism between samples. Results: We demonstrate various results from applying TestDimorph functions to data supplied with the package. Discussion: The package has many features including functionality for working with summary statistics, simulating data from summary statistics, and the extraction of summary statistics from raw data, so that the entire analysis can be performed through the package.
MeSH term(s)	Male ; Female ; Humans ; Sex Characteristics ; Multivariate Analysis ; Analysis of Variance ; Normal Distribution ; Phenotype
Language	English
Publishing date	2023-09-11
Publishing country	United States
Document type	Journal Article
ISSN	2692-7691
ISSN (online)	2692-7691
DOI	10.1002/ajpa.24842
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Article ; Online: Epigenetics and sarcoidosis.

Konigsberg, Iain R / Maier, Lisa A / Yang, Ivana V

European respiratory review : an official journal of the European Respiratory Society

2021 Volume 30, Issue 160

Abstract: Epigenetic modifications are emerging as important regulatory mechanisms of gene expression in lung disease, given that they are influenced by environmental exposures and genetic variants, and that they regulate immune and fibrotic processes. In this ... ...

Abstract	Epigenetic modifications are emerging as important regulatory mechanisms of gene expression in lung disease, given that they are influenced by environmental exposures and genetic variants, and that they regulate immune and fibrotic processes. In this review, we introduce these concepts with a focus on the study of DNA methylation and histone modifications and discuss how they have been applied to lung disease, and how they can be applied to sarcoidosis. This information has implications for other exposure and immunologically mediated lung diseases, such as chronic beryllium disease, hypersensitivity pneumonitis, and asbestosis.
MeSH term(s)	DNA Methylation ; Environmental Exposure ; Epigenesis, Genetic ; Humans ; Lung Diseases ; Sarcoidosis/diagnosis ; Sarcoidosis/genetics
Language	English
Publishing date	2021-06-23
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1077620-5
ISSN	1600-0617 ; 0905-9180
ISSN (online)	1600-0617
ISSN	0905-9180
DOI	10.1183/16000617.0076-2021
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Article ; Online: Skeletal muscle DNA methylation: Effects of exercise and HIV.

Jankowski, Catherine M / Konigsberg, Iain R / Wilson, Melissa P / Sun, Jing / Brown, Todd T / Julian, Colleen G / Erlandson, Kristine M

Aging cell

2023 Volume 23, Issue 1, Page(s) e14025

Abstract: Aging, human immunodeficiency virus (HIV) infection, and antiretroviral therapy modify the epigenetic profile and function of cells and tissues, including skeletal muscle (SkM). In some cells, accelerated epigenetic aging begins very soon after the ... ...

Abstract	Aging, human immunodeficiency virus (HIV) infection, and antiretroviral therapy modify the epigenetic profile and function of cells and tissues, including skeletal muscle (SkM). In some cells, accelerated epigenetic aging begins very soon after the initial HIV infection, potentially setting the stage for the early onset of frailty. Exercise imparts epigenetic modifications in SkM that may underpin some health benefits, including delayed frailty, in people living with HIV (PWH). In this first report of exercise-related changes in SkM DNA methylation among PWH, we investigated the impact of 24 weeks of aerobic and resistance exercise training on SkM (vastus lateralis) DNA methylation profiles and epigenetic age acceleration (EAA) in older, virally suppressed PWH (n = 12) and uninfected controls (n = 18), and associations of EAA with physical function at baseline. We identified 983 differentially methylated positions (DMPs) in PWH and controls at baseline and 237 DMPs after training. The influence of HIV serostatus on SkM methylation was more pronounced than that of exercise training. There was little overlap in the genes associated with the probes most significantly differentiated by exercise training within each group. Baseline EAA (mean ± SD) was similar between PWH (-0.4 ± 2.5 years) and controls (0.2 ± 2.6 years), and the exercise effect was not significant (p = 0.79). EAA and physical function at baseline were not significantly correlated (all p ≥ 0.10). This preliminary investigation suggests HIV-specific epigenetic adaptations in SkM with exercise training but confirmation in a larger study that includes transcriptomic analysis is warranted.
MeSH term(s)	Humans ; Aged ; DNA Methylation/genetics ; Frailty/genetics ; HIV Infections/genetics ; Epigenesis, Genetic/genetics ; Exercise/physiology ; Muscle, Skeletal/metabolism ; Aging/genetics
Language	English
Publishing date	2023-11-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2113083-8
ISSN	1474-9726 ; 1474-9718
ISSN (online)	1474-9726
ISSN	1474-9718
DOI	10.1111/acel.14025
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Article: Proteomic Networks and Related Genetic Variants Associated with Smoking and Chronic Obstructive Pulmonary Disease.

Konigsberg, Iain R / Vu, Thao / Liu, Weixuan / Litkowski, Elizabeth M / Pratte, Katherine A / Vargas, Luciana B / Gilmore, Niles / Abdel-Hafiz, Mohamed / Manichaikul, Ani W / Cho, Michael H / Hersh, Craig P / DeMeo, Dawn L / Banaei-Kashani, Farnoush / Bowler, Russell P / Lange, Leslie A / Kechris, Katerina J

medRxiv : the preprint server for health sciences

2024

Abstract: Background: Studies have identified individual blood biomarkers associated with chronic obstructive pulmonary disease (COPD) and related phenotypes. However, complex diseases such as COPD typically involve changes in multiple molecules with ... ...

Abstract	Background: Studies have identified individual blood biomarkers associated with chronic obstructive pulmonary disease (COPD) and related phenotypes. However, complex diseases such as COPD typically involve changes in multiple molecules with interconnections that may not be captured when considering single molecular features. Methods: Leveraging proteomic data from 3,173 COPDGene Non-Hispanic White (NHW) and African American (AA) participants, we applied sparse multiple canonical correlation network analysis (SmCCNet) to 4,776 proteins assayed on the SomaScan v4.0 platform to derive sparse networks of proteins associated with current vs. former smoking status, airflow obstruction, and emphysema quantitated from high-resolution computed tomography scans. We then used NetSHy, a dimension reduction technique leveraging network topology, to produce summary scores of each proteomic network, referred to as NetSHy scores. We next performed genome-wide association study (GWAS) to identify variants associated with the NetSHy scores, or network quantitative trait loci (nQTLs). Finally, we evaluated the replicability of the networks in an independent cohort, SPIROMICS. Results: We identified networks of 13 to 104 proteins for each phenotype and exposure in NHW and AA, and the derived NetSHy scores significantly associated with the variable of interests. Networks included known (sRAGE, ALPP, MIP1) and novel molecules (CA10, CPB1, HIS3, PXDN) and interactions involved in COPD pathogenesis. We observed 7 nQTL loci associated with NetSHy scores, 4 of which remained after conditional analysis. Networks for smoking status and emphysema, but not airflow obstruction, demonstrated a high degree of replicability across race groups and cohorts. Conclusions: In this work, we apply state-of-the-art molecular network generation and summarization approaches to proteomic data from COPDGene participants to uncover protein networks associated with COPD phenotypes. We further identify genetic associations with networks. This work discovers protein networks containing known and novel proteins and protein interactions associated with clinically relevant COPD phenotypes across race groups and cohorts.
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.26.24303069
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Article: Multi-Omic Signatures of Sarcoidosis and Progression in Bronchoalveolar Lavage Cells.

Konigsberg, Iain R / Lin, Nancy W / Liao, Shu-Yi / Liu, Cuining / MacPhail, Kristyn / Mroz, Margaret M / Davidson, Elizabeth / Restrepo, Clara I / Sharma, Sunita / Li, Li / Maier, Lisa A / Yang, Ivana V

bioRxiv : the preprint server for biology

2023

Abstract: Introduction: Sarcoidosis is a heterogeneous, granulomatous disease that can prove difficult to diagnose, with no accurate biomarkers of disease progression. Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify ... ...

Abstract	Introduction: Sarcoidosis is a heterogeneous, granulomatous disease that can prove difficult to diagnose, with no accurate biomarkers of disease progression. Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify molecular changes associated with sarcoidosis and disease progression that might illuminate underlying mechanisms of disease and potential genomic biomarkers. Methods: Bronchoalveolar lavage cells from 64 sarcoidosis subjects and 16 healthy controls were used. DNA methylation was profiled on Illumina HumanMethylationEPIC arrays, mRNA by RNA-sequencing, and miRNAs by small RNA-sequencing. Linear models were fit to test for effect of diagnosis and phenotype, adjusting for age, sex, and smoking. We built a supervised multi-omics model using a subset of features from each dataset. Results: We identified 46,812 CpGs, 1,842 mRNAs, and 5 miRNAs associated with sarcoidosis versus controls and 1 mRNA, Conclusions: Leveraging the DNA methylome, transcriptome, and miRNA-sequencing in sarcoidosis BAL cells, we detected widespread molecular changes associated with disease, many which are involved in immune response. These molecules may serve as diagnostic/prognostic biomarkers and/or drug targets, although future testing will be required for confirmation.
Language	English
Publishing date	2023-01-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.26.525601
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Article: SmCCNet 2.0: A Comprehensive Tool for Multi-omics Network Inference with Shiny Visualization.

Liu, Weixuan / Vu, Thao / Konigsberg, Iain / Pratte, Katherine / Zhuang, Yonghua / Kechris, Katerina

bioRxiv : the preprint server for biology

2024

Abstract: ... Availability: This package is available in both CRAN: https://cran.r-project.org/web/packages/SmCCNet/index ...

Abstract	Summary: Sparse multiple canonical correlation network analysis (SmCCNet) is a machine learning technique for integrating omics data along with a variable of interest (e.g., phenotype of complex disease), and reconstructing multi-omics networks that are specific to this variable. We present the second-generation SmCCNet (SmCCNet 2.0) that adeptly integrates single or multiple omics data types along with a quantitative or binary phenotype of interest. In addition, this new package offers a streamlined setup process that can be configured manually or automatically, ensuring a flexible and user-friendly experience. Availability: This package is available in both CRAN: https://cran.r-project.org/web/packages/SmCCNet/index.html and Github: https://github.com/KechrisLab/SmCCNet under the MIT license. The network visualization tool is available at https://smccnet.shinyapps.io/smccnetnetwork/.
Language	English
Publishing date	2024-04-07
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.20.567893
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Article ; Online: Multiomic Signatures of Chronic Beryllium Disease Bronchoalveolar Lavage Cells Relate to T-Cell Function and Innate Immunity.

Li, Li / Konigsberg, Iain R / Bhargava, Maneesh / Liu, Sucai / MacPhail, Kristyn / Mayer, Annyce / Davidson, Elizabeth J / Liao, Shu-Yi / Lei, Zhe / Mroz, Peggy M / Fingerlin, Tasha E / Yang, Ivana V / Maier, Lisa A

American journal of respiratory cell and molecular biology

2022 Volume 67, Issue 6, Page(s) 632–640

Abstract: Chronic beryllium disease (CBD) is a Th1 granulomatous lung disease preceded by sensitization to beryllium (BeS). We profiled the methylome, transcriptome, and selected proteins in the lung to identify molecular signatures and networks associated with ... ...

Abstract	Chronic beryllium disease (CBD) is a Th1 granulomatous lung disease preceded by sensitization to beryllium (BeS). We profiled the methylome, transcriptome, and selected proteins in the lung to identify molecular signatures and networks associated with BeS and CBD. BAL cell DNA and RNA were profiled using microarrays from CBD (
MeSH term(s)	Humans ; Berylliosis/genetics ; T-Lymphocytes ; Bronchoalveolar Lavage ; Bronchoalveolar Lavage Fluid ; Immunity, Innate/genetics ; RNA ; Chronic Disease
Chemical Substances	BES (10191-18-1) ; RNA (63231-63-0)
Language	English
Publishing date	2022-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1025960-0
ISSN	1535-4989 ; 1044-1549
ISSN (online)	1535-4989
ISSN	1044-1549
DOI	10.1165/rcmb.2022-0077OC
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Article ; Online: Single-cell RNA sequencing identifies macrophage transcriptional heterogeneities in granulomatous diseases.

Liao, Shu-Yi / Atif, Shaikh M / Mould, Kara / Konigsberg, Iain R / Fu, Rui / Davidson, Elizabeth / Li, Li / Fontenot, Andrew P / Maier, Lisa A / Yang, Ivana V

The European respiratory journal

2021 Volume 57, Issue 6

MeSH term(s)	Granuloma ; Humans ; Macrophages ; Sequence Analysis, RNA
Language	English
Publishing date	2021-06-17
Publishing country	England
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.03794-2020
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