Machine-learning-driven biomarker discovery for the discrimination between allergic and irritant contact dermatitis

Contact dermatitis tremendously impacts the quality of life of suffering patients. Currently, diagnostic regimes rely on allergy testing, exposure specification, and follow-up visits; however, distinguishing the clinical phenotype of irritant and allergic contact dermatitis remains challenging. Employing integrative transcriptomic analysis and machine-learning approaches, we aimed to decipher disease-related signature genes to find suitable sets of biomarkers. A total of 89 positive patch-test reaction biopsies against four contact allergens and two irritants were analyzed via microarray. Coexpression network analysis and Random Forest classification were used to discover potential biomarkers and selected biomarker models were validated in an independent patient group. Differential gene-expression analysis identified major gene-expression changes depending on the stimulus. Random Forest classification identified CD47, BATF, FASLG, RGS16, SYNPO, SELE, PTPN7, WARS, PRC1, EXO1, RRM2, PBK, RAD54L, KIFC1, SPC25, PKMYT, HISTH1A, TPX2, DLGAP5, TPX2, CH25H, and IL37 as potential biomarkers to distinguish allergic and irritant contact dermatitis in human skin. Validation experiments and prediction performances on external testing datasets demonstrated potential applicability of the identified biomarker models in the clinic. Capitalizing on this knowledge, novel diagnostic tools can be developed to guide clinical diagnosis of contact allergies.Peer reviewe

Cohort profile : InTraUterine sampling in early pregnancy (ITU), a prospective pregnancy cohort study in Finland: study design and baseline characteristics

Purpose The InTraUterine sampling in early pregnancy (ITU) is a prospective pregnancy cohort study. The overarching aim of ITU is to unravel genomic, epigenomic, transcriptomic, endocrine, inflammatory and metabolic maternal-placental-fetal mechanisms involved in the programming of health and disease after exposure to prenatal environmental adversity, such as maternal malnutrition, cardiometabolic disorders, infections, medical interventions, mental disorders and psychosocial stress. This paper describes the study protocol, design and baseline characteristics of the cohort. Participants We included 944 pregnant Finnish women, their partners and children born alive between April 2012 and December 2017. The women were recruited through the national, voluntary trisomy 21 screening between 9(+0) and 21(+6) gestational weeks. Of the participating women, 543 were screen positive and underwent fetal chromosomal testing. Test result of these women suggested no fetal chromosomal abnormality. Further, we recruited 401 women who were screen negative and who did not undergo fetal chromosomal testing. Findings to date We have collected chorionic villi and amniotic fluid from the screen-positive women; blood, urine, buccal swabs and diurnal salivary samples from all women; blood and buccal swabs from all partners; and placenta, cord blood and buccal swabs from all newborns for analyses of the genome, epigenome, transcriptome, and endocrine, inflammatory and metabolic markers. These data are coupled with comprehensive phenotypes, including questions on demographic characteristics, health and well-being of the women and their partners during pregnancy and of the women and their children at the child's age of 1.7 and 3 years. Data also come from patient records and nationwide registers covering health, lifestyle and medication data. Future plans Multiple layers of ITU data allow integrative data analyses, which translate to biomarker identification and allow risk stratification and understanding of the biological mechanisms involved in prenatal programming of health and disease.Peer reviewe

Soil exposure modifies the gut microbiota and supports immune tolerance in a mouse model

Background: Sufficient exposure to natural environments, in particular soil and its microbes, has been suggested to be protective against allergies. Objective: We aim at gaining more direct evidence of the environment-microbiota-health axis by studying the colonization of gut microbiota in mice after exposure to soil and by examining immune status in both a steady-state situation and during allergic inflammation. Methods: The gastrointestinal microbiota of mice housed on clean bedding or in contact with soil was analyzed by using 16S rRNA gene sequencing, and the data were combined with immune parameters measured in the gut mucosa, lung tissue, and serum samples. Results: We observed marked differences in the small intestinal and fecal microbiota composition between mice housed on clean bedding or in contact with soil, with a higher proportion of Bacteroidetes relative to Firmicutes in the soil group. The housing environment also influenced mouse intestinal gene expression, as shown by upregulated expression of the immunoregulatory markers IL-10, forkhead box P3, and cytotoxic T lymphocyte-associated protein 4 in the soil group. Importantly, using the murine asthma model, we found that exposure to soil polarizes the immune system toward T(H)1 and a higher level of anti-inflammatory signaling, alleviating T(H)2-ype allergic responses. The inflammatory status of the mice had a marked influence on the composition of the gut microbiota, suggesting bidirectional communication along the gut-lung axis. Conclusion: Our results provide evidence of the role of environmentally acquired microbes in alleviating against T(H)2-driven inflammation, which relates to allergic diseases.Peer reviewe

Interplay between skin microbiota and immunity in atopic individuals

Funding Information: This research was supported by Jane & Aatos Erkko Foundation.Non peer reviewe

Cohort profile: InTraUterine sampling in early pregnancy (ITU), a prospective pregnancy cohort study in Finland: Study design and baseline characteristics

Purpose The InTraUterine sampling in early pregnancy (ITU) is a prospective pregnancy cohort study. The overarching aim of ITU is to unravel genomic, epigenomic, transcriptomic, endocrine, inflammatory and metabolic maternal-placental-fetal mechanisms involved in the programming of health and disease after exposure to prenatal environmental adversity, such as maternal malnutrition, cardiometabolic disorders, infections, medical interventions, mental disorders and psychosocial stress. This paper describes the study protocol, design and baseline characteristics of the cohort. Participants We included 944 pregnant Finnish women, their partners and children born alive between April 2012 and December 2017. The women were recruited through the national, voluntary trisomy 21 screening between 9 +0 and 21 +6 gestational weeks. Of the participating women, 543 were screen positive and underwent fetal chromosomal testing. Test result of these women suggested no fetal chromosomal abnormality. Further, we recruited 401 women who were screen negative and who did not undergo fetal chromosomal testing. Findings to date We have collected chorionic villi and amniotic fluid from the screen-positive women; blood, urine, buccal swabs and diurnal salivary samples from all women; blood and buccal swabs from all partners; and placenta, cord blood and buccal swabs from all newborns for analyses of the genome, epigenome, transcriptome, and endocrine, inflammatory and metabolic markers. These data are coupled with comprehensive phenotypes, including questions on demographic characteristics, health and well-being of the women and their partners during pregnancy and of the women and their children at the child's age of 1.7 and 3 years. Data also come from patient records and nationwide registers covering health, lifestyle and medication data. Future plans Multiple layers of ITU data allow integrative data analyses, which translate to biomarker identification and allow risk stratification and understanding of the biological mechanisms involved in prenatal programming of health and disease

Cohort profile:InTraUterine sampling in early pregnancy (ITU), a prospective pregnancy cohort study in Finland:study design and baseline characteristics

Abstract Purpose: The InTraUterine sampling in early pregnancy (ITU) is a prospective pregnancy cohort study. The overarching aim of ITU is to unravel genomic, epigenomic, transcriptomic, endocrine, inflammatory and metabolic maternal-placental-fetal mechanisms involved in the programming of health and disease after exposure to prenatal environmental adversity, such as maternal malnutrition, cardiometabolic disorders, infections, medical interventions, mental disorders and psychosocial stress. This paper describes the study protocol, design and baseline characteristics of the cohort. Participants: We included 944 pregnant Finnish women, their partners and children born alive between April 2012 and December 2017. The women were recruited through the national, voluntary trisomy 21 screening between 9+0 and 21+6 gestational weeks. Of the participating women, 543 were screen positive and underwent fetal chromosomal testing. Test result of these women suggested no fetal chromosomal abnormality. Further, we recruited 401 women who were screen negative and who did not undergo fetal chromosomal testing. Findings to date: We have collected chorionic villi and amniotic fluid from the screen-positive women; blood, urine, buccal swabs and diurnal salivary samples from all women; blood and buccal swabs from all partners; and placenta, cord blood and buccal swabs from all newborns for analyses of the genome, epigenome, transcriptome, and endocrine, inflammatory and metabolic markers. These data are coupled with comprehensive phenotypes, including questions on demographic characteristics, health and well-being of the women and their partners during pregnancy and of the women and their children at the child’s age of 1.7 and 3 years. Data also come from patient records and nationwide registers covering health, lifestyle and medication data. Future plans: Multiple layers of ITU data allow integrative data analyses, which translate to biomarker identification and allow risk stratification and understanding of the biological mechanisms involved in prenatal programming of health and disease