| 1. |
- Hildebrandt, Franziska, 1994-, et al.
(författare)
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Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the mouse liver
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Reconstruction of heterogeneity through single cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we apply Spatial Transcriptomics to perform transcriptomic analysis across sectioned liver tissue. We confirm that the heterogeneity in this complex tissue is predominantly determined by lobular zonation. By introducing novel computational approaches, we enable transcriptional gradient measurements between tissue structures, including several lobules in a variety of orientations. Further, our data suggests the presence of previously transcriptionally uncharacterized structures within liver tissue, contributing to the overall spatial heterogeneity of the organ. This study demonstrates how comprehensive spatial transcriptomic technologies can be used to delineate extensive spatial gene expression patterns in the liver, indicating its future impact for studies of liver function, development and regeneration as well as its potential in pre-clinical and clinical pathology. Global transcriptional differences across lobular units in the liver remain unknown. Here the authors perform spatial transcriptomics of liver tissue to delineate transcriptional differences in physical space, confirm lobular zonation along transcriptional gradients and suggest the presence of previously uncharacterized structures within liver tissue.
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| 2. |
- Öhman, May-Britt, 1966-, et al.
(författare)
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Sámi Land Free University : An invitation to centre Indigenous Peoples expertise and knowledge in an online open access university
- 2023
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Konferensbidrag (refereegranskat)abstract
- This roundtable aims at presenting what the platform Sámi Land Free University (SFU) has achieved so far and to invite to a conversation on what SFU may achieve in the practice of decolonising research and education, while inviting interested to join forces for courses and joint or shared research over the colonial borders.Over the last four decades, Indigenous Studies (IS) has been developed as an academic discipline within several settler colonial states and within colonial academia, the strongest presence in North America, Australia and Aotearoa/New Zealand. So far Sweden is lagging behind. Yet, IS mainly turns the gaze towards the Indigenous peoples, while to achieve decolonization and long term sustainability, as well as good relations, there is a need for a 180 degrees shift in vision. What if there were several universities that centre Indigenous knowledges and expertise, as point of departure, while researching and teaching for the benefit of all?In 2015, the SFU [www.samelandsfriauniversitet.com ] was created by Lule and Forest Sámi, Dr May-Britt Ӧhman with a vision and challenge of the mind to include the Sámi community and international Indigenous collaborations, having its base on the Swedish side of Sábme. SFU has co-hosted symposia and workshops. We now envision moving on, producing free to access online educational content, inviting earlier and new collaborators. Methods adopted are supra-disciplinary, giving voice to academics, artists, and practitioners of Indigenous ways of knowing and being, while also inviting other scientific methods. Commentator: Kim TallBear, Univ of Alberta, Faculty of Native Studies1 May-Britt Öhman, Lule and Forest Sámi, with Tornedalian heritage, SábmeCentre for Multidisciplinary Studies on Racism, Uppsala UniversityExperiences from the last 7 years with the platform Sámi Land Free University – what has it done for my – and others – thinking and acting?Introductory presentation on how the Sámi Land Free University came about as a website in 2015, followed by a Facebook page, a youtube channel, and some of the activities that has taken place, as well as some thoughts on possibilities to move ahead.There are so far very little opportunities for Sámi to study our own history, culture, traditions, epistemologies at universities in Sweden. There are even less opportunities to have a place in academia for Sámi who are open with their Sámi identity. Hence, there is a need for a place to gather, to develop courses, and proposed ways to make this happen, as the (settler colonial) academia so far gives very little space to Sámi perspectives in Sweden. Yet, Swedish legislation states that the Sámi are a people, with rights, and that Sámi history, culture and tradition shall be taught to pupils in school and secondary school.Furthermore, at universities, there is almost no teaching on Indigenous peoples culture, history, traditions, around the world, while the settler colonial perspectives are taught in all university courses.Thus, there is a need for a Sámi university, on Swedish side of Sábme, that will provide both Sámi and other Indigenous peoples history, traditions, culture, expertise, perspectives - the question is mainly how to organize this.2 Frances Wyld, Martu woman (Aboriginal People of the Pilbara region of Australia) living on Kaurna land, Dr of CommunicationJustice and Society, University of South AustraliaAll good thing are wild and free: the wild winds that carried me to Sámi Land Free University.NAISA introduced me to the international cross fertilization of ideas within Indigenous research and education, specifically it created the opportunity to collaborate with Sámi Land Free University as an Australian Aboriginal scholar. The collaboration has included 6 visits to Sweden and Sápmi for symposia and workshops, publications, and freelance work on a climate change and Indigenous sustainability project. I am a storyteller; I write in the moment inspired by nature. I watch the news reporting on the damage done by wild winds on the weekend. The reporter is in front of a house where a tree has fallen onto it, the house is on my road. At the same time, through my open door, I hear the whine of the chainsaw cutting into this majestic ghost gum tree. Only weeks ago, I was riding my bicycle along the same road with a wild sense of freedom as my birds, the Rainbow Lorikeets who live in the avenue of trees, flew alongside me. Sámi Land Free University has given me the same sense of freedom to work as a decolonising scholar within Critical Indigenous Studies, gaining international perspectives and walking on two lands that are both rich is stories. The collaboration has given me opportunities, and now in the spirit of reciprocity, I lend my skills as a curriculum developer to create content for this grassroots university in another land inhabited by Indigenous people who have much in common with my own people, with knowledges to share for a sustainable future.3 Anna Kajsa Aira and Laila Susanna Kuhmunen, Jokkmokk in collaboration with Alma Linke NilsenDuv gábdde - Du gákti - Din kolt – Your Sámi dressWe are Sámi artisans, duojár. Anna Kajsa makes handicraft – duodje - in the Lule Sámi tradition, Jokkmokk area. Laila Susanna works within the North Sámi duodji tradition of the Karesuando area. We both live in Jokkmokk/Jåhkåmåhkke, a Sámi metropolis. Sámi heritage is passed down from generation to generation.The traditional Sámi dress – gábbde/gákti/kolt - reveals one’s geographical area and is an important link to one’s roots and history. Many Sámi now reclaim their culture by wanting to wear the dress, but there is a gap of one generation in the transmission of knowledge about how to make them. Our project “your Sámi dress” is about providing this knowledge, both by making the gábbde for children and young people, for rent, and through making a digital platform with instructions and advice. It is just as important to be able to wear your gábbde as it is to handle it respectfully. While there is a university in Sweden for textiles and fashion, there is no such for Sámi culture. We think maybe our work could find a place within the SFU, and thereby receive more support. 4 Henrik Andersson and Hampus Andersson, Gällivare Forest Sámi villageExperiences of and reflections on the needs for education and higher education for and about Sámi reindeer herdersReindeer husbandry is carried out on Sámi territories, on almost 50 percent of the territories of the colonial state of Sweden. It is is a tradition – a way of life – as well as a basis for livelihood, income, since several hundred of years. It is acknowledged as a national interest, to be protected, since 1987.Yet, the knowledge and expertise of reindeer herding is mainly passed within the families. Learning demands spending time together with the older generations, from early childhood. As the school system requests pupils to be in school, this often come into conflict with the need to learn. Furthermore, for a reindeer herder, there are an increasing set of other skills than the actual herding – which is complex enough- that are of importance; economics, law, animal health, and one’s own history and culture etc. In school, secondary school, and at universities, there are no opportunities to study reindeer herding with the other skills thereto related. Another aspect of the education system’s lack of teaching on reindeer and reindeer herding, is that when persons within the reindeer herding meet with all parts of society – health care, police, teachers, social care, etc, they have to carry the burden of constantly educating them, and also facing discrimination and racism. Henrik , 42 years old, and Hampus , 20 years old, are two generations reindeer herders within the Gällivare Forest Sámi village, Flakaberg group. They will share their experiences and reflect on the need for education and higher education for Sámi reindeer herders. 5 Susanne Spik and Gun Aira, Jåhkåmåkke in collaboration with Alma Linke NilsenLule Sámi culture and language on university level ? Experiences, reflections and ideas Gun Aira is a Lule Sámi teacher and Susanne Spik, is an entrepreneur and innovator. Both live in Jåhkåmåhkke, and are active within reindeer herding. Both have attended university – teacher’s education- at a Swedish university, in the 1980s. The Lule Sámi language and culture origin in the Lule River valley. Due to the by the Swedish state forced relocation of several North Sámi families, from the Karesuando area during in the 20th century, along with fierce Swedification politics, both the language and culture have become sidestepped. While there is a Lule Sámi centre on Norwegian side, there is no such on the Swedish. In general, there is vastly more support to Sámi culture and language in Norway, than in Sweden. We will present our experiences, reflections and ideas on how SFU could be of use to promote Lule Sámi language and culture, and wish to develop this with the others and the audience.
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| 3. |
- Almroth, Melody, et al.
(författare)
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Job control, job demands and job strain and suicidal behaviour among three million workers in Sweden
- 2022
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 79:10, s. 681-689
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the association between job control, job demands and their combination (job strain) and suicide attempts and deaths among male and female workers in Sweden.Methods Job control and demands were measured separately for men and women using a job exposure matrix, which was linked to around three million individuals based on their occupational title in 2005. Suicide attempts and deaths were measured in the hospital and cause of death registers from 2006 to 2016. HRs were estimated using discrete proportional hazards models with annually updated age as the time axis. Models were adjusted for sociodemographic, family, health, labour market and childhood factors, as well as the time-varying effects of unemployment, sick leave and family factors during follow-up.Results Low job control was associated with an increased risk of suicide attempts and deaths among both men and women while high job demands tended to be associated with a decreased risk. The combination of job control and job demands (job strain) reflected the increased risk of low control jobs and the decreased risk of high demand jobs. Associations were attenuated but still present after adjustments.Conclusions Low job control is related to suicide attempts and deaths, and this is only partially explained by important covariates measured both prebaseline and during follow-up. Attempts to increase job control among workers may be beneficial in preventing suicide.
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| 4. |
- Andersson, Alma
(författare)
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A Landmark-based Common Coordinate Framework for Spatial Transcriptomics Data
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The increasing amount of spatial transcriptomics data prompts for means to amalgamate observations from distinct experiments, especially attractive is to cast quantities from different sources into a common coordinate frame-work (CCF) to relate signals across space. We here present a method that enables transfer of information from multiple samples to a reference representing a CCF, and show its utility by analyzing an assortment of real and synthetic data sets.
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| 5. |
- Andersson, Alma, 1995-
(författare)
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Computational methods for analysis of spatial transcriptomics data : An exploration of the spatial gene expression landscape
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Transcriptomics techniques, whether in the form of bulk, single cell/nuclei, or spatial methods have fueled a substantial expansion of our knowledge about the biological systems within and around us. In addition, the rate of innovation has accelerated over the last decade, resulting in a multitude of technological advances and new methods for generation of transcriptomics data. In 2009, isolating and characterizing the transcriptome of a single cell was seen as a major achievement, ten years later, in 2019, studies surveying a hundred thousand cells were commonplace. The field of spatial transcriptomics went through an equally transformative phase; from struggling with simultaneous characterization of a few targets, to seamlessly provide spatially resolved maps of the full transcriptome. Inevitably, we’re approaching an inflection point where the generation of data is no longer the bottleneck, but rather its analysis. Alas, with standardized commercial products, high-quality spatial transcriptomics data can now be generated en masse. Hence, questions about data analysis have started to replace those of data generation. The work in this thesis seeks to address some of these emerging questions; the five articles it encompasses presents new methods for analysis of spatial transcriptomics data and examples of their application. Furthermore, it contains an introduction to current experimental and computational spatial transcriptomics techniques, as well as a section about data modeling. In Article I, a probabilistic model for integration of single cell/nuclei and spatial transcriptomics data is presented. In short, the method allows for mixed signals – present in certain spatial transcriptomics platforms – to be decomposed into contributions from biologically relevant cell types or states derived from single cell/nuclei data. The model was implemented in code as a software, stereoscope, which is open source and publicly available. The same policy of open source and high transparency holds true for all software or code associated with this thesis. The stereoscope method has been used in several studies, one example being Article II, where we examined the spatial transcriptomics landscape of HER2-positive breast cancer patients. By integrating single cell and spatial transcriptomics data, several intriguing co-localization signals emerged. These signals allowed us to identify a signature for tertiary lymphoid structures and evidence of a trifold interaction involving: type I interferon signals, a T-cell subset, and a macrophage subset. However, the work also included other forms of explorative data analysis, such as unsupervised expression-based clustering. The clusters from this analysis, once annotated, exhibited high concordance with annotations provided by a pathologist and the tissue morphology. Taken together, this makes a compelling case for the use of spatial transcriptomics in the age of “digital pathology.” Finally, we also derived “core signatures” from the expression-based clusters, representing common expression profiles shared across the patients.In Article III, we present a computational method, sepal, designed to identify genes with distinct spatial patterns, often referred to as “spatially variable genes.” The method uses Fick’s second law to simulate diffusion of transcripts in the tissue, measuring the time until convergence (a spatially uniform and homogeneous state). It then ranks the genes by their “diffusion time.” The assumption being that genes exhibiting strong spatial patterns will take longer time to converge compared to genes with no pattern, thus relating the diffusion time to the degree of spatial structure. Article IV constitutes a study of the mouse liver using spatial transcriptomics. As before, we employed stereoscope for the purpose of single cell integration, but realized more tailored computational tools – towards the specific tissue – were required to address certain questions. Thus, we developed two computational methods, one devoted to vein type identity prediction, the other enabling a change of data representation. In essence, to predict the vein identities, we first assembled spatially weighted composite expression profiles from – to the vein – neighboring observations. Then, a logistic classifier was trained using the composite profiles. Once the model was trained, it could be used to assign vein type identities to ambiguous or unannotated veins. In the second method, the two-dimensional spatial data was recast into a more informative one-dimensional representation by treating gene expression as a function of an observation’s distance to its nearest vein structure.The final work, Article V, expands the idea of recasting data into a more informative or helpful representation. More precisely, we present a method, eggplant, that allows the user to transfer spatial transcriptomics data from multiple sources to a common coordinate framework (CCF). Transfer of information to a CCF means spatial signals can be compared across conditions and time points, unlocking a plethora of valuable downstream analyses. For example, we perform spatiotemporal modeling of a synthetic system, and introduce the concept of “spatial arithmetics” to study local expression differences. With a growing corpus of spatial trancsriptomics data and ambitious international efforts like the Human Cell Atlas, we deem these sort of methods essential to leverage the data’s full potential.
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| 6. |
- Andersson, Alma E. V., et al.
(författare)
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Exploring the Viral Channel Kcv(PBCV-1) Function via Computation
- 2018
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Ingår i: Journal of Membrane Biology. - : SPRINGER. - 0022-2631 .- 1432-1424. ; 251:3, s. 419-430
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Tidskriftsartikel (refereegranskat)abstract
- Viral potassium channels (Kcv) are homologous to the pore module of complex -selective ion channels of cellular organisms. Due to their relative simplicity, they have attracted interest towards understanding the principles of conduction and channel gating. In this work, we construct a homology model of the open state, which we validate by studying the binding of known blockers and by monitoring ion conduction through the channel. Molecular dynamics simulations of this model reveal that the re-orientation of selectivity filter carbonyl groups coincides with the transport of potassium ions, suggesting a possible mechanism for fast gating. In addition, we show that the voltage sensitivity of this mechanism can originate from the relocation of potassium ions inside the selectivity filter. We also explore the interaction of with the surrounding bilayer and observe the binding of lipids in the area between two adjacent subunits. The model is available to the scientific community to further explore the structure/function relationship of Kcv channels.
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| 7. |
- Andersson, Alma, et al.
(författare)
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sepal : identifying transcript profiles with spatial patterns by diffusion-based modeling
- 2021
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811 .- 1460-2059. ; 37:17, s. 2644-2650
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Collection of spatial signals in large numbers has become a routine task in multiple omics-fields, but parsing of these rich datasets still pose certain challenges. In whole or near-full transcriptome spatial techniques, spurious expression profiles are intermixed with those exhibiting an organized structure. To distinguish profiles with spatial patterns from the background noise, a metric that enables quantification of spatial structure is desirable. Current methods designed for similar purposes tend to be built around a framework of statistical hypothesis testing, hence we were compelled to explore a fundamentally different strategy. Results: We propose an unexplored approach to analyze spatial transcriptomics data, simulating diffusion of individual transcripts to extract genes with spatial patterns. The method performed as expected when presented with synthetic data. When applied to real data, it identified genes with distinct spatial profiles, involved in key biological processes or characteristic for certain cell types. Compared to existing methods, ours seemed to be less informed by the genes' expression levels and showed better time performance when run with multiple cores.
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| 8. |
- Andersson, Alma, et al.
(författare)
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Single-cell and spatial transcriptomics enables probabilistic inference of cell type topography
- 2020
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Ingår i: Communications Biology. - : Nature Research. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- The field of spatial transcriptomics is rapidly expanding, and with it the repertoire of available technologies. However, several of the transcriptome-wide spatial assays do not operate on a single cell level, but rather produce data comprised of contributions from a – potentially heterogeneous – mixture of cells. Still, these techniques are attractive to use when examining complex tissue specimens with diverse cell populations, where complete expression profiles are required to properly capture their richness. Motivated by an interest to put gene expression into context and delineate the spatial arrangement of cell types within a tissue, we here present a model-based probabilistic method that uses single cell data to deconvolve the cell mixtures in spatial data. To illustrate the capacity of our method, we use data from different experimental platforms and spatially map cell types from the mouse brain and developmental heart, which arrange as expected.
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| 9. |
- Andersson, Alma, et al.
(författare)
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Spatial deconvolution of HER2-positive breast cancer delineates tumor-associated cell type interactions
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- In the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra- and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. By integration with single cell data, we spatially map tumor-associated cell types to find tertiary lymphoid-like structures, and a type I interferon response overlapping with regions of T-cell and macrophage subset colocalization. We construct a predictive model to infer presence of tertiary lymphoid-like structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define a high resolution map of cellular interactions in tumors and provide tools generalizing across tissues and diseases. While transcriptomics have enhanced our understanding for cancer, spatial transcriptomics enable the characterisation of cellular interactions. Here, the authors integrate single cell data with spatial information for HER2 + tumours and develop tools for the prediction of interactions between tumour-infiltrating cells.
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| 10. |
- Andersson, Alma, et al.
(författare)
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Spatial Deconvolution of HER2-positive Breast Tumors Reveals Novel Intercellular Relationships
- 2020
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra-and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. We integrate and spatially map tumor-associated types from single cell data to find: segregated epithelial cells, interactions between B and T-cells and myeloid cells, co-localization of macrophage and T-cell subsets. A model is constructed to infer presence of tertiary lymphoid structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define novel interactions between tumor-infiltrating cells in breast cancer and provide tools generalizing across tissues and diseases.
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