Browsing by Author "Siljander, Heli"

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  • Characterization and non-parametric modeling of the developing serum proteome during infancy and early childhood
    (2018-12-01) Lietzén, Niina; Cheng, Lu; Moulder, Robert; Siljander, Heli; Laajala, Essi; Härkönen, Taina; Peet, Aleksandr; Vehtari, Aki; Tillmann, Vallo; Knip, Mikael; Lähdesmäki, Harri; Lahesmaa, Riitta
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    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 3-36 months. A flexible Gaussian process-based probabilistic modelling framework was developed to evaluate the effects of different variables, including age, living environment and individual variation, on the longitudinal expression profiles of 266 reliably identified and quantified serum proteins. Age was the most dominant factor influencing approximately half of the studied proteins, and the most prominent age-associated changes were observed already during the first year of life. High inter-individual variability was also observed for multiple proteins. These data provide important details on the maturing serum proteome during early life, and evaluate how patterns detected in cord blood are conserved in the first years of life. Additionally, our novel modelling approach provides a statistical framework to detect associations between covariates and non-linear time series data.
  • Early detection of peripheral blood cell signature in children developing β-cell autoimmunity at a young age
    (2019-10-01) Kallionpää, Henna; Somani, Juhi; Tuomela, Soile; Ullah, Ubaid; De Albuquerque, Rafael; Lönnberg, Tapio; Komsi, Elina; Siljander, Heli; Honkanen, Jarno; Härkönen, Taina; Peet, Aleksandr; Tillmann, Vallo; Chandra, Vikash; Anagandula, Mahesh Kumar; Frisk, Gun; Otonkoski, Timo; Rasool, Omid; Lund, Riikka; Lähdesmäki, Harri; Knip, Mikael; Lahesmaa, Riitta
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a clear and urgent need for new biomarkers that predict the onset of the autoimmune reaction preceding autoantibody positivity or reflect progressive β-cell destruction. Here we report the mRNA sequencing-based analysis of 306 samples including fractionated samples of CD4+ and CD8+ T cells as well as CD4-CD8- cell fractions and unfractionated peripheral blood mononuclear cell samples longitudinally collected from seven children who developed β-cell autoimmunity (case subjects) at a young age and matched control subjects. We identified transcripts, including interleukin 32 (IL32), that were upregulated before T1D-associated autoantibodies appeared. Single-cell RNA sequencing studies revealed that high IL32 in case samples was contributed mainly by activated T cells and NK cells. Further, we showed that IL32 expression can be induced by a virus and cytokines in pancreatic islets and β-cells, respectively. The results provide a basis for early detection of aberrations in the immune system function before T1D and suggest a potential role for IL32 in the pathogenesis of T1D.
  • Genomic variation and strain-specific functional adaptation in the human gut microbiome during early life
    (2019-03-01) Vatanen, Tommi; Plichta, Damian R.; Somani, Juhi; Münch, Philipp C.; Arthur, Timothy D.; Hall, Andrew Brantley; Rudolf, Sabine; Oakeley, Edward J.; Ke, Xiaobo; Young, Rachel A.; Haiser, Henry J.; Kolde, Raivo; Yassour, Moran; Luopajärvi, Kristiina; Siljander, Heli; Virtanen, Suvi M.; Ilonen, Jorma; Uibo, Raivo; Tillmann, Vallo; Mokurov, Sergei; Dorshakova, Natalya; Porter, Jeffrey A.; McHardy, Alice C.; Lähdesmäki, Harri; Vlamakis, Hera; Huttenhower, Curtis; Knip, Mikael; Xavier, Ramnik J.
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    The human gut microbiome matures towards the adult composition during the first years of life and is implicated in early immune development. Here, we investigate the effects of microbial genomic diversity on gut microbiome development using integrated early childhood data sets collected in the DIABIMMUNE study in Finland, Estonia and Russian Karelia. We show that gut microbial diversity is associated with household location and linear growth of children. Single nucleotide polymorphism- and metagenomic assembly-based strain tracking revealed large and highly dynamic microbial pangenomes, especially in the genus Bacteroides, in which we identified evidence of variability deriving from Bacteroides-targeting bacteriophages. Our analyses revealed functional consequences of strain diversity; only 10% of Finnish infants harboured Bifidobacterium longum subsp. infantis, a subspecies specialized in human milk metabolism, whereas Russian infants commonly maintained a probiotic Bifidobacterium bifidum strain in infancy. Groups of bacteria contributing to diverse, characterized metabolic pathways converged to highly subject-specific configurations over the first two years of life. This longitudinal study extends the current view of early gut microbial community assembly based on strain-level genomic variation.