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Characterization of developing proteome during early childhood

ABSTRACT: Children develop rapidly during the first years of life, and understanding the different sources and levels of variation in serum proteome of young children is important when using serum proteins as markers for childhood diseases. We have performed label/free quantitative proteomics for longitudinal serum samples collected from a group of children during the first years of life.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

SUBMITTER: Niina Lietzen

LAB HEAD: Riitta Lahesmaa

PROVIDER: PXD006775 | Pride | 2018-04-18

REPOSITORIES: Pride

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			Action	DRS
	Child10_0_1.raw	Raw
	Child10_0_2.raw	Raw
	Child10_0_3.raw	Raw
	Child10_12_1.raw	Raw
	Child10_12_2.raw	Raw

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Publications

Characterization and non-parametric modeling of the developing serum proteome during infancy and early childhood.

Lietzén Niina N Cheng Lu L Moulder Robert R Siljander Heli H Laajala Essi E Härkönen Taina T Peet Aleksandr A Vehtari Aki A Tillmann Vallo V Knip Mikael M Lähdesmäki Harri H Lahesmaa Riitta R

Scientific reports 20180412 1

Children develop rapidly during the first years of life, and understanding the sources and associated levels of variation in the serum proteome is important when using serum proteins as markers for childhood diseases. The aim of this study was to establish a reference model for the evolution of a healthy serum proteome during early childhood. Label-free quantitative proteomics analyses were performed for 103 longitudinal serum samples collected from 15 children at birth and between the ages of 3 ...[more]

PMID: 29650987

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Expression data from childhood obesity

Project description:In the past few decades, the prevalence of overweight and obesity has sharply increased in children and adolescents. Childhood obesity life are associated with increased risk of cardiovascular disease (CVD), diabetes mellitus, metabolic syndrome, sleep disturbances and certain cancers in adulthood. Childhood obesity has become a serious global public health challenge. Long noncoding RNAs (lncRNAs) have an important role in adipose tissue function and energy metabolism homeostasis, and abnormalities may lead to obesity. We used microarrays to detail the differential expression profile of lncRNAs and mRNAs in obese children compared with non-obese children.

2018-06-14 | GSE104815 | GEO

DNA methylation in blood from neonatal screening cards and the association with BMI and insulin sensitivity in early childhood

Project description:There is increasing evidence that metabolic diseases originate in early life, and epigenetic changes have been implicated as key drivers of this early life programming. This led to the hypothesis that epigenetic marks present at birth may predict an individual’s future risk of obesity and type 2 diabetes. In this study, we assessed whether epigenetic marks in blood of newborn children were associated with BMI and insulin sensitivity later in childhood. DNA methylation was measured in neonatal blood spot samples of 439 children using the Illumina Infinium 450k BeadChip. Associations were assessed between DNA methylation at birth and BMI z-scores, body fat mass, fasting plasma glucose, insulin and HOMA-IR at age 5 years, as well as birthweight, maternal BMI and smoking status. No individual methylation sites at birth were associated with obesity or insulin sensitivity measures at 5 years. DNA methylation in 69 genomic regions at birth was associated with BMI z-scores at age 5 years, and in 63 regions with HOMA-IR. The methylation changes were generally small (<5%), except for a region near the non-coding RNA nc886 (VTRNA2-1) where a clear link between methylation status at birth and BMI in childhood was observed (P=0.001). Associations were also found between DNA methylation, maternal smoking, and birth weight. We identified a number of DNA methylation regions at birth that were associated with obesity or insulin sensitivity measurements in childhood. These findings support the mounting evidence on the role of epigenetics in programming of metabolic health. Whether many of these small changes in DNA methylation are causally related to the health outcomes, and of clinical relevance, remains to be determined, but the nc886 region represents a promising obesity risk marker that warrants further investigation.

2017-09-09 | GSE103657 | GEO

Transcriptional landscape of human adipose tissue in infancy and childhood

Project description:Incidence of obesity is increasingly prevalent among children: global pediatric obesity incidence raised by 30% globally in the last two decades and increased tenfold in the last four decades. Being obese as a child increases the likelihood of being obese as an adult, and suffer from obesity-related health complications. Adipose tissue development in the first year of life may determine adiposity in early childhood. Our aim is to understand mechanisms that control healthy adipose tissue development from infancy to childhood. We collected adipose tissue specimens during elective surgery from the inguinal region of human infants and children, with normal BMI and without known metabolic or endocrine diseases. Samples were proceesed for extraction of total RNA, using phenol:chlorophorm extraction. Next generation RNA sequencing were performed.

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Thermal proteome profiling of childhood ALL cell lines for proteoform detection

Project description:Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and it has a 5-year survival rate of 85% for European children. But for subsets of patients who fail to respond to standard of care chemotherapeutics, treatment options are limited, and clinical prognosis is poor. To establish a novel platform and methodology to better characterize ALL subtypes and identify their pharmacologic vulnerabilities, we performed thermal proteome profiling of 20 childhood ALL cell lines.

2023-03-20 | PXD031162 | Pride

Site-specific development and progressive maturation of human tissue resident memory T cells over infancy and childhood

Project description:Infancy and childhood are critical life stages for the generation of immune memory for protection against pathogens. This process has been challenging to elucidate in humans as most memory T cells reside in tissues. Here, we define localization, and developmental pathways of memory T cells in mucosal sites, lymphoid tissues, and blood from pediatric donors aged 0-10 years. We reveal that memory T cells preferentially localize in mucosal sites during infancy and accumulate more rapidly over childhood compared to blood and lymphoid organs. Mucosal memory T cells in infancy exhibit stem-like transcriptional profiles, but progressively adopt signatures of mature tissue resident memory T cells over childhood. Our results show that exposures during the formative years establish the landscape of immunity through tissue-specific generation and adaptation of memory T cells

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Genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma

Project description:Asthma is caused by a combination of poorly understood genetic and environmental factors. We found multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P < 10-12. In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in EBV-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P <10-22) in cis with transcript levels of ORMDL3, a member of a gene family that encode transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma. Experiment Overall Design: Gene expression levels were evaluated in 404 children. We then evaluated the relationship between SNPs in the 17q21 region (which show association to asthma in the same children) with gene expression levels. See http://www.sph.umich.edu/csg/liang/asthma/

2007-11-09 | E-GEOD-8052 | biostudies-arrayexpress

Genome-scale DNA methylation profiling of TEL/AML positive childhood acute lymphoblastic leukaemia

Project description:DNA methylation profiling of 48 samples to determine a DNA methylation signature specific to leukaemic bone marrow samples. Matching Leukaemia bone marrow and day 28 remission bone marrow or post induction follow up (follow up up to 2 years post induction) genomic DNA were extracted from archived microscope smear slides from 11 children diagnosed with TEL/AML positive Acute Lymphoblastic Leukaemia (ALL). Unmatched bone marrow samples from an additional 8 children were also analysed. Primary tissue control samples from CD34+ and CD19+ bone marrow from adult and childhood samples as well as model cell lines (cancer and non cancerous) were compared to primary diseased samples. Disease specific DNA methylation changes were identified from these results and then verified using SEQUENOM EpiTYPER. A total of 48 samples were analysed by Infinium DNA methylation analysis. As per manufacturer's protocols. Replicates were performed on one primary tumour sample and one cell line sample.

2012-12-31 | E-GEOD-29189 | biostudies-arrayexpress

Genome-scale DNA methylation profiling of TEL/AML positive childhood acute lymphoblastic leukaemia

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Associations between IFI44L gene variants and rates of respiratory tract infections during early childhood

Project description:Background: Genetic heterogeneity in the innate immune system may account for variable susceptibility to respiratory tract infections (RTIs) in children. Objective: We aimed to assess the impact of polymorphisms rs273259 and rs1333969 in type I interferon related gene IFI44L on susceptibility to RTIs and acute otitis media in children. Methods: In two prospective, population-based birth cohorts, the FinnBrain Birth Cohort Study and the STEPS Study, IFI44L genotypes for rs273259 and rs1333969 were determined in relation to the development of RTIs until one and two years of age, respectively, and adjusted incidence rate ratios (aIRR) or odds ratios (OR) were calculated. At age 3 months, whole blood transcriptional profiles were analyzed and nasal samples were tested for respiratory viruses in a subset of children. Results: In respiratory virus-positive children at 3 months of age, IFI44L gene variants were associated with decreased expression levels of IFI44L and several other interferon related genes. Conclusions: Variant forms of IFI44L gene were protective against early-childhood RTIs or acute otitis media in two independent birth cohorts, and they attenuated interferon pathway activation by respiratory viruses.

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Transcription profiling of human diagnostic samples from children with NCI high risk B-precursor ALL treated on the protocol COG 1961 to investigate early response and outcome in high-risk childhood acute lymphoblastic leukemia

Project description:The cure rate for childhood ALL has improved considerably in part because therapy is routinely tailored to the predicted risk of relapse. Various clinical and laboratory variables are used in current risk-stratification schemes, but many children who fail therapy lack adverse prognostic factors at initial diagnosis. Using gene expression analysis, we have identified genes and pathways in a NCI high-risk childhood B-precursor ALL cohort at diagnosis that may play a role in early blast regression as correlated with the Day 7 marrow status. We have also identified a 47-probeset signature (representing 41 unique genes) that was predictive of long term outcome in our dataset as well as three large independent datasets of childhood ALL treated on different protocols. Experiment Overall Design: Diagnostic marrow samples from 99 children with NCI high risk B-precursor ALL treated on the protocol COG 1961 were analyzed. To study genetic profiles associated with early response to therapy, 82 of the total 99 patients were analyzed: 42 patients with a M1 marrow at day 7 of therapy were compared to 40 patients with a M3 marrow at day 7. To study the genes associated with long-term outcome, expression profiles of 59 (of the total 99) patients were analyzed: 28 patients who remained in complete continuous remission (CCR) for at least 4 years and 31 patients who suffered a bone marrow relapse within the first 3 years of initial diagnosis. Forty-two patients were common in both the early response and outcome analyses.

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