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This thesis shows a viable machine learning model that detects Indoor or Outdoor on smartphones. The model was designed as a classification problem and it was trained with data collected from several smartphone sensors by participants of a field trial conducted. The data collected was labeled manually either indoor or outdoor by the participants themselves. The model was then iterated over to lower the energy consumption by utilizing feature selection techniques and subsampling techniques. The model which uses all of the data achieved a 99 % prediction accuracy, while the energy efficient model achieved 92.91 %. This work provides the tools for researchers to quantify environmental exposure using smartphones.

Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic beta cells. beta cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in beta cell gene regulation and diabetes, the function of beta cell lncRNAs remains largely unknown. In this study, we investigated the function of beta cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate b cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key b cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of beta cell-specific transcription factor networks.

Understanding the regulation of pancreatic development is key for efforts to develop new regenerative therapeutic approaches for diabetes. Rare mutations in PDX1 and PTF1A can cause pancreatic agenesis, however, most instances of this disorder are of unknown origin. We report de novo heterozygous inactivating mutations in GATA6 in 15/27 (56%) individuals with pancreatic agenesis. These findings define the most common cause of human pancreatic agenesis and establish a key role for the transcription factor GATA6 in human pancreatic development.

Summary Despite the central role of chromosomal context in gene transcription, human noncoding DNA variants are generally studied outside of their genomic location. This limits our understanding of disease-causing regulatory variants. INS promoter mutations cause recessive neonatal diabetes. We show that all INS promoter point mutations in 60 patients disrupt a CC dinucleotide, whereas none affect other elements important for episomal promoter function. To model CC mutations, we humanized an ∼3.1-kb region of the mouse Ins2 gene. This recapitulated developmental chromatin states and cell-specific transcription. A CC mutant allele, however, abrogated active chromatin formation during pancreas development. A search for transcription factors acting through this element revealed that another neonatal diabetes gene product, GLIS3, has a pioneer-like ability to derepress INS chromatin, which is hampered by the CC mutation. Our in vivo analysis, therefore, connects two human genetic defects in an essential mechanism for developmental activation of the INS gene., Graphical abstract, Highlights • Mutations of a CC dinucleotide in the human INS promoter cause neonatal diabetes • We humanized ∼3.1 kb of mouse Ins2 and created a CC mutant version • Humanized Ins2, but not the CC mutant, recapitulates developmental chromatin activation • GLIS3, also mutated in diabetes, activates INS chromatin and requires an intact CC, Mutations in the CC element of the INS promoter or the transcription factor GLIS3 cause neonatal diabetes. Akerman et al. humanize a 3.1-kb region upstream of the mouse Ins2 gene and show that GLIS3 and the CC element form a pioneering mechanism that activates INS chromatin during pancreas development.

Summary Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks., Graphical Abstract, Highlights • A loss-of-function screen reveals functional β cell lncRNAs • Cell-specific lncRNAs and transcription factors regulate common gene networks • The lncRNA PLUTO influences interactions between an enhancer cluster and PDX1 • PLUTO and PDX1 are deregulated in type 2 diabetes and impaired glucose tolerance, Akerman et al. studied the function of human β cell lncRNAs with RNAi, CRISPRi, and co-expression networks. This revealed β cell lncRNAs and transcription factors that control common regulatory networks. One lncRNA, PLUTO, is downregulated in type 2 diabetes and controls PDX1, encoding a key β cell transcription factor.