Machine learning unveils an immune-related DNA methylation profile in germline DNA from breast cancer patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE243529 | GEO | 2024/05/16
REPOSITORIES: GEO
Similar Datasets
Project description:(1) In clinical practice and biomedical research populations are often divided categorically into distinct racial and ethnic groups. In reality, these categories comprise diverse groups with highly heterogeneous histories, cultures, traditions, religions, as well as social and environmental exposures. While the factors captured by these categories contribute to clinical practice and biomedical research, the use of race/ethnicity is widely debated. As a response to this debate, genetic ancestry has been suggested as a complement or alternative to this categorization. However, few studies have examined the effect of genetic ancestry, racial/ethnic identity, and environmental exposures on biological processes. Herein, we examine the contribution of self-identification within ethnicity, genetic ancestry, and environmental exposures on epigenetic modification of DNA methylation, a phenomenon affected by both genetic and environmental factors. We typed over 450,000 variably methylated CpG sites in primary whole blood of 573 individuals of Mexican and Puerto Rican descent who also had high-density genotype data. We found that methylation levels at a large number of CpG sites were significantly associated with ethnicity even when adjusting for genetic ancestry. In addition, we found an enrichment of ethnicity-associated sites amongst loci previously associated with environmental and social exposures. Interestingly, one of the strongest associated sites is driven by the Duffy Null blood type variant, demonstrating a new function of the locus in lymphocytes. Overall, the methylation changes associated with race/ethnicity, driven by both genes and environment, highlight the importance of measuring and accounting for both self-identified race/ethnicity and genetic ancestry in clinical and biomedical studies and the benefits of studying diverse populations. (2) In epigenome-wide association studies (EWAS), different methylation profiles of distinct cell-types may lead to false discoveries. We introduce ReFACTor, a method based on principal component analysis (PCA) for the correction of cell-type heterogeneity in EWAS. ReFACTor does not require knowledge of the cell counts, and it obtains improved estimates of the cell-type composition, resulting in improved power and control for false positives in EWAS.
2016-02-29 | GSE77716 | GEO
Project description:(1) In clinical practice and biomedical research populations are often divided categorically into distinct racial and ethnic groups. In reality, these categories comprise diverse groups with highly heterogeneous histories, cultures, traditions, religions, as well as social and environmental exposures. While the factors captured by these categories contribute to clinical practice and biomedical research, the use of race/ethnicity is widely debated. As a response to this debate, genetic ancestry has been suggested as a complement or alternative to this categorization. However, few studies have examined the effect of genetic ancestry, racial/ethnic identity, and environmental exposures on biological processes. Herein, we examine the contribution of self-identification within ethnicity, genetic ancestry, and environmental exposures on epigenetic modification of DNA methylation, a phenomenon affected by both genetic and environmental factors. We typed over 450,000 variably methylated CpG sites in primary whole blood of 573 individuals of Mexican and Puerto Rican descent who also had high-density genotype data. We found that methylation levels at a large number of CpG sites were significantly associated with ethnicity even when adjusting for genetic ancestry. In addition, we found an enrichment of ethnicity-associated sites amongst loci previously associated with environmental and social exposures. Interestingly, one of the strongest associated sites is driven by the Duffy Null blood type variant, demonstrating a new function of the locus in lymphocytes. Overall, the methylation changes associated with race/ethnicity, driven by both genes and environment, highlight the importance of measuring and accounting for both self-identified race/ethnicity and genetic ancestry in clinical and biomedical studies and the benefits of studying diverse populations. (2) In epigenome-wide association studies (EWAS), different methylation profiles of distinct cell-types may lead to false discoveries. We introduce ReFACTor, a method based on principal component analysis (PCA) for the correction of cell-type heterogeneity in EWAS. ReFACTor does not require knowledge of the cell counts, and it obtains improved estimates of the cell-type composition, resulting in improved power and control for false positives in EWAS. Bisulphite converted DNA from 573 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip and a complete blood count with automated white blood cell differential was performed by automated flow cytometry for 95 of the samples.
2016-02-29 | E-GEOD-77716 | biostudies-arrayexpress
Project description:The discovery of blood-based proteomics biomarkers is recently a popular topic in AD studies due to its advantage to relate external environmental factors with the development of AD. In this study, a proteomic study based on Malaysian Chinese and Malay prospects was conducted. Differentially expressed proteins (DEPs) in AD patients and normal controls for Chinese and Malays were identified. The dissimilarities of dysregulated proteins identified in Chinese and Malays samples suggested the differences of pathways involved in this pathological condition for each respective ethnicity: the Chinese group was involved to Aβ/tau protein-related, oxidative stress and inflammation whereas neuroinflammation was related to the Malays. These findings served as a preliminary understanding in the molecular studies of AD especially in multi-ethnic population.
2024-06-10 | PXD040566 | Pride
Project description:In the United States, African-American (AA) women are more likely to develop early-onset breast cancer and have historically poorer outcomes due to this disease compared to European-American (EA) women. Here, we analyzed genomic profiles of breast tumors from young women (<50 years old), matched by tumor subtype, histological grade, and ethnicity (African-American, AA, compared to European-American, EA). DNA copy number alterations (CNAs) were analyzed on the Affymetrix Human SNP Array v 6.0 platform. The study provides insight into the genetic component of ethnicity-related breast cancer health disparities.
2013-01-29 | GSE26232 | GEO
Project description:In the United States, African-American (AA) women are more likely to develop early-onset breast cancer and have historically poorer outcomes due to this disease compared to European-American (EA) women. Here, we analyzed genomic profiles of breast tumors from young women (<50 years old), matched by tumor subtype, histological grade, and ethnicity (African-American, AA, compared to European-American, EA). DNA copy number alterations (CNAs) were analyzed using a 32K BAC tiling path array. The study provides insight into the genetic component of ethnicity-related breast cancer health disparities.
2013-01-29 | GSE26214 | GEO
Project description:In the United States, African-American (AA) women are more likely to develop early-onset breast cancer and have historically poorer outcomes due to this disease compared to European-American (EA) women. Here, we analyzed genomic profiles of breast tumors from young women (<50 years old), matched by tumor subtype, histological grade, and ethnicity (African-American, AA, compared to European-American, EA). DNA copy number alterations (CNAs) were analyzed using a 32K BAC tiling path array. The study provides insight into the genetic component of ethnicity-related breast cancer health disparities. Breast tumor samples from young women (< 50 years old) were matched as follows: a matched pair consists of one AA and one EA sample, matched for tumor grade and tumor subtype (based on immunohistochemical analysis of ER, PR, and HER2 status). 44 experiments; each experiment is tumor DNA versus reference control DNA (AF) isolated from the blood of a 25-year-old African-American female with no familial or personal history of breast cancer. Additional control experiments included the AF reference versus the well-characterized F1 reference, and 3 self-self hybridization controls (AF versus AF).
2013-01-29 | E-GEOD-26214 | biostudies-arrayexpress
Project description:<p>The genome-wide association study (GWAS) includes participants enrolled into two different studies. The first study, the San Francisco Bay Area Cancer Study (SFBCS) is a population-based case-control study of breast cancer conducted in the San Francisco Bay Area and included women ages 35-79 years from three racial/ethnic groups: Non-Hispanic whites, African Americans, and Hispanics/Latinas. For the GWAS, only Hispanic/Latina women were included. Women diagnosed with invasive breast cancer between 1995 and 2002 were identified through the Greater Bay Area Cancer Registry. Controls were identified by random digit dialing and were frequency-matched to cases by age in 5 year increments and by race/ethnicity. Hispanic/Latina ethnicity was assessed by self-report. 175 Hispanic/Latina cases and 307 Hispanic/Latina controls from the SFBCS had given adequate consent and provided biospecimens that were used in the GWAS to be included in this data submission.</p> <p>The second study is the Northern California site of the Breast Cancer Family Registry (NC-BCFR). This population-based family study recruited breast cancer cases ages 18-64 years diagnosed from 1995-2009 that were identified through the Greater Bay Area Cancer Registry. Cases included all women at increased genetic susceptibility for breast cancer who met one or more of the following criteria: (a) being diagnosed with breast cancer at age <35 years; b) having a personal history of ovarian cancer or childhood cancer; (c) being diagnosed with two different breast cancers (bilateral breast cancers), with the first one diagnosed at age <50 years; and d) having one or more first-degree relatives with breast cancer, ovarian cancer or childhood cancer. Cases not meeting these criteria were randomly sampled and racial/ethnic minorities were oversampled. Controls were recruited by random digit dialing and were matched by 5-year age increments and by race/ethnicity. For the current GWAS only Latina/Hispanic cases and controls were included. Latina/Hispanic ethnicity was assessed by self-report. 631 Hispanic/Latina cases and 61 Hispanic/Latina controls from the NC-BCFR had given adequate consent and provided biospecimens that were used in the GWAS to be included in this data submission.</p>
| phs000912 | dbGaP
Project description:The mortality risk from cancer-associated sepsis is differentially affected by individual cancer sites and host responses to sepsis are heterogenous. Native Hawaiians have a 2-fold higher mortality risk from cancer-associated sepsis than Whites and also higher mortality risk from colorectal cancer (CRC). We investigated this disparity by examining ethnic variation in the transcriptome of patients with CRC-associated sepsis and its relation to survival and genetic diversity. We conducted transcriptomic profiling of CRC tumors and adjacent non-tumor tissue obtained from adult patients of Native Hawaiian and Japanese ethnicity who died from cancer-associated sepsis. We examined differential gene expression in relation to patient survival and sepsis disease etiology.
2022-09-01 | GSE198103 | GEO
Project description:Genome wide DNA methylation profiling of blood samples collected from patients after diagnosis with hepatocellular carcinoma (HCC) (cases) vs. blood samples collected from healthy individuals without family history of cancer (controls). The Illumina Infinium 450K Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 450,000 CpGs in human samples corresponding to cases (post-diagnostic HCC) and controls. Samples included 24 cases and 24 controls. Cases were matched with controls on gender, age, ethnicity, hepatitis C infection, and diabetes. The presence or absence of HCC in our study was determined based on the AASLD criteria.
2022-01-31 | GSE113409 | GEO
Project description:Gene expression profiles were generated from 199 primary breast cancer patients. Samples 1-176 were used in another study, GEO Series GSE22820, and form the training data set in this study. Sample numbers 200-222 form a validation set. This data is used to model a machine learning classifier for Estrogen Receptor Status. RNA was isolated from 199 primary breast cancer patients. A machine learning classifier was built to predict ER status using only three gene features.
2013-01-01 | E-GEOD-29210 | biostudies-arrayexpress