Bioinformatics approaches for the analysis of lipidomics data

The potential impact of lipid research has been increasingly realised both in disease treatment and prevention. Recent advances in soft ionization mass spectrometry (MS) such as electrospray ionization (ESI) have permitted parallel monitoring of several hundreds of lipids in a single experiment and thus facilitated lipidomics level studies. These advances, however, pose a greater challenge for bioinformaticians to handle massive amounts of information-rich MS data from modern analytical instruments in order to understand complex functions of lipids. The main aims of this thesis were to 1) develop bioinformatics approaches for lipid identification based on ultra performance liquid chromatography coupled to mass spectrometry (UPLC/MS) data, 2) predict the functional annotations for unidentified lipids, 3) understand the omics data in the context of pathways and 4) apply existing chemometric methods for exploratory data analysis as well as biomarker discovery. A bioinformatics strategy for the construction of lipid database for major classes of lipids is presented using simplified molecular input line entry system (SMILES) approach. The database was annotated with relevant information such as lipid names including short names, SMILES information, scores, molecular weight, monoisotopic mass, and isotope distribution. The database was tailored for UPLC/MS experiments by incorporating the information such as retention time range, adduct information and main fragments to screen for the potential lipids. This database information facilitated building experimental tandem mass spectrometry libraries for different biological tissues. Non-targeted metabolomics screening is often get plagued by the presence of unknown peaks and thus present an additional challenge for data interpretation. Multiple supervised classification methods were employed and compared for the functional prediction of class labels for unidentified lipids to facilitate exploratory analysis further as well as ease the identification process. As lipidomics goes beyond complete characterization of lipids, new strategies were developed to understand lipids in the context of pathways and thereby providing insights for the phenotype characterization. Chemometric methods such as principal component analysis (PCA) and partial least squares and discriminant analysis (PLS/DA) were utilised for exploratory analysis as well as biomarker discovery in the context of different disease phenotypes

Automaattisen sisällönkuvailun ohjelmiston rakentaminen – case Annif

Sisällönkuvailun automatisointiratkaisut ovat puhuttaneet kirjastomaailmassa viime vuosina, ja erilaisia kokeiluja on tehty niin Suomessa kuin maailmallakin. Kansalliskirjastossa kehitetty automaattisen sisällönkuvailun Annif-työkalu on herättänyt paljon mielenkiintoa monissa organisaatioissa ja kokemukset ensimmäisistä käyttöönotoista ovat olleet lupaavia. Mitä kehitysvalintoja Annifia rakennettaessa on tehty, ja minkälaisia haasteita kuvailun automatisointiin ylipäätään liittyy

Bioinformatics approaches for the analysis of lipidomics data

SUMMARY The events that contribute to the expansion of -cell mass and enhanced -cell function in insulin-resistant states have not been elucidated fully. Recently, we showed that -cell adaptation failed dramatically in adult, insulin-resistant POKO mice, which contrasts with the appropriate expansion of cells in their ob/ob littermates. Thus, we hypothesised that characterisation of the islets in these mouse models at an early age should provide a unique opportunity to: (1) identify mechanisms involved in sensing insulin resistance at the level of the cells, (2) identify molecular effectors that contribute to increasing -cell mass and function, and (3) distinguish primary events from secondary events that are more likely to be present at more advanced stages of diabetes. Our results define the POKO mouse as a model of early lipotoxicity. At 4 weeks of age, it manifests with inappropriate -cell function and defects in proliferation markers. Other well-recognised pathogenic effectors that were observed previously in 16-week-old mice, such as increased reactive oxygen species (ROS), macrophage infiltration and endoplasmic reticulum (ER) stress, are also present in both young POKO and young ob/ob mice, indicating the lack of predictive power with regards to the severity of -cell failure. Of interest, the relatively preserved lipidomic profile in islets from young POKO mice contrasted with the large changes in lipid composition and the differences in the chain length of triacylglycerols in the serum, liver, muscle and adipose tissue in adult POKO mice. Later lipotoxic insults in adult cells contribute to the failure of the POKO cell. Our results indicate that the rapid development of insulin resistance and -cell failure in POKO mice makes this model a useful tool to study early molecular events leading to insulin resistance and -cell failure. Furthermore, comparisons with ob/ob mice might reveal important adaptive mechanisms in cells with either therapeutic or diagnostic potential