Studies on sequencing analyses of genetic and epigenetics features in melanoma and breast cancer

The dissertation includes 3 projects and in each work we applied different approaches to sequencing and bioinformatics analyses to gain a better understanding of the molecular characteristics of breast cancer and melanoma. In the first project (paper I) we applied whole exome sequencing to samples from patients with metastatic melanoma. We assessed intra patient heterogeneity and we identified several general patterns of tumor evolution in this malignancy. In the second project (paper II) we used promoter methylation-specific sequencing and analysed the variation of promoter methylation of tumor suppressors in healthy individuals. As such, we also established a cost-effective method to study promoter methylation as a potential modulator of cancer risk. In the third project (paper III), we used microRNA sequencing and identified novel miRNAs that were overexpressed in breast cancer patients. Two of these were selected for further investigation focusing on their potential biological roles in breast cancer.Doktorgradsavhandlin

Dynamic Time-Lag Regression: Predicting what & when

This paper tackles a new regression problem, called Dynamic Time-Lag Regression (DTLR), where a cause signal drives an effect signal with an unknown time delay. The motivating application, pertaining to space weather modelling, aims to predict the near-Earth solar wind speed based on estimates of the Sun’s coronal magnetic field. DTLR differs from mainstream regression and from sequence-to-sequence learning in two respects: firstly, no ground truth (e.g., pairs of associated sub-sequences) is available; secondly, the cause signal contains much information irrelevant to the effect signal (the solar magnetic field governs the solar wind propagation in the heliosphere, of which the Earth’s magnetosphere is but a minuscule region).A Bayesian approach is presented to tackle the specifics of the DTLR problem,with theoretical justifications based on linear stability analysis. A proof of concept on synthetic problems is presented. Finally, the empirical results on the solar wind modelling task improve on the state of the art in solar wind forecasting

Heliophysics Discovery Tools for the 21st Century: Data Science and Machine Learning Structures and Recommendations for 2020-2050

Three main points: 1. Data Science (DS) will be increasingly important to heliophysics; 2. Methods of heliophysics science discovery will continually evolve, requiring the use of learning technologies [e.g., machine learning (ML)] that are applied rigorously and that are capable of supporting discovery; and 3. To grow with the pace of data, technology, and workforce changes, heliophysics requires a new approach to the representation of knowledge.Comment: 4 pages; Heliophysics 2050 White Pape

Observations of the 2019 April 4 Solar Energetic Particle Event at the Parker Solar Probe

A solar energetic particle event was detected by the Integrated Science Investigation of the Sun (IS⊙IS) instrument suite on Parker Solar Probe (PSP) on 2019 April 4 when the spacecraft was inside of 0.17 au and less than 1 day before its second perihelion, providing an opportunity to study solar particle acceleration and transport unprecedentedly close to the source. The event was very small, with peak 1 MeV proton intensities of ~0.3 particles (cm² sr s MeV)⁻¹, and was undetectable above background levels at energies above 10 MeV or in particle detectors at 1 au. It was strongly anisotropic, with intensities flowing outward from the Sun up to 30 times greater than those flowing inward persisting throughout the event. Temporal association between particle increases and small brightness surges in the extreme-ultraviolet observed by the Solar TErrestrial RElations Observatory, which were also accompanied by type III radio emission seen by the Electromagnetic Fields Investigation on PSP, indicates that the source of this event was an active region nearly 80° east of the nominal PSP magnetic footpoint. This suggests that the field lines expanded over a wide longitudinal range between the active region in the photosphere and the corona

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

AI-ready data in space science and solar physics: problems, mitigation and action plan

In the domain of space science, numerous ground-based and space-borne data of various phenomena have been accumulating rapidly, making analysis and scientific interpretation challenging. However, recent trends in the application of artificial intelligence (AI) have been shown to be promising in the extraction of information or knowledge discovery from these extensive data sets. Coincidentally, preparing these data for use as inputs to the AI algorithms, referred to as AI-readiness, is one of the outstanding challenges in leveraging AI in space science. Preparation of AI-ready data includes, among other aspects: 1) collection (accessing and downloading) of appropriate data representing the various physical parameters associated with the phenomena under study from different repositories; 2) addressing data formats such as conversion from one format to another, data gaps, quality flags and labeling; 3) standardizing metadata and keywords in accordance with NASA archive requirements or other defined standards; 4) processing of raw data such as data normalization, detrending, and data modeling; and 5) documentation of technical aspects such as processing steps, operational assumptions, uncertainties, and instrument profiles. Making all existing data AI-ready within a decade is impractical and data from future missions and investigations exacerbates this. This reveals the urgency to set the standards and start implementing them now. This article presents our perspective on the AI-readiness of space science data and mitigation strategies including definition of AI-readiness for AI applications; prioritization of data sets, storage, and accessibility; and identifying the responsible entity (agencies, private sector, or funded individuals) to undertake the task

Observations of the 2019 April 4 Solar Energetic Particle Event at the Parker Solar Probe

A solar energetic particle event was detected by the Integrated Science Investigation of the Sun (IS⊙IS) instrument suite on Parker Solar Probe (PSP) on 2019 April 4 when the spacecraft was inside of 0.17 au and less than 1 day before its second perihelion, providing an opportunity to study solar particle acceleration and transport unprecedentedly close to the source. The event was very small, with peak 1 MeV proton intensities of ~0.3 particles (cm² sr s MeV)⁻¹, and was undetectable above background levels at energies above 10 MeV or in particle detectors at 1 au. It was strongly anisotropic, with intensities flowing outward from the Sun up to 30 times greater than those flowing inward persisting throughout the event. Temporal association between particle increases and small brightness surges in the extreme-ultraviolet observed by the Solar TErrestrial RElations Observatory, which were also accompanied by type III radio emission seen by the Electromagnetic Fields Investigation on PSP, indicates that the source of this event was an active region nearly 80° east of the nominal PSP magnetic footpoint. This suggests that the field lines expanded over a wide longitudinal range between the active region in the photosphere and the corona

Observations of the 2019 April 4 Solar Energetic Particle Event at the Parker Solar Probe

A solar energetic particle event was detected by the Integrated Science Investigation of the Sun (ISOIS) instrument suite on Parker Solar Probe (PSP) on 2019 April 4 when the spacecraft was inside of 0.17 au and less than 1 day before its second perihelion, providing an opportunity to study solar particle acceleration and transport unprecedentedly close to the source. The event was very small, with peak 1 MeV proton intensities of ~0.3 particles (cm^2 sr s MeV)^-1, and was undetectable above background levels at energies above 10 MeV or in particle detectors at 1 au. It was strongly anisotropic, with intensities flowing outward from the Sun up to 30 times greater than those flowing inward persisting throughout the event. Temporal association between particle increases and small brightness surges in the extreme-ultraviolet observed by the Solar TErrestrial RElations Observatory, which were also accompanied by type III radio emission seen by the Electromagnetic Fields Investigation on PSP, indicates that the source of this event was an active region nearly 80 degrees east of the nominal PSP magnetic footpoint. This suggests that the field lines expanded over a wide longitudinal range between the active region in the photosphere and the corona

Basement membrane components are key players in specialized extracellular matrices

More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration, and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized, opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components with a special emphasis on embryonic and adult stem cells and their niches