| 1. |
|
|
| 2. |
|
|
| 3. |
- Berglund, Emelie, et al.
(författare)
-
Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.
|
|
| 4. |
- Chelebian, Eduard, et al.
(författare)
-
Morphological Features Extracted by AI Associated with Spatial Transcriptomics in Prostate Cancer
- 2021
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:19
-
Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Prostate cancer has very varied appearances when examined under the microscope, and it is difficult to distinguish clinically significant cancer from indolent disease. In this study, we use computer analyses inspired by neurons, so-called 'neural networks', to gain new insights into the connection between how tissue looks and underlying genes which program the function of prostate cells. Neural networks are 'trained' to carry out specific tasks, and training requires large numbers of training examples. Here, we show that a network pre-trained on different data can still identify biologically meaningful regions, without the need for additional training. The neural network interpretations matched independent manual assessment by human pathologists, and even resulted in more refined interpretation when considering the relationship with the underlying genes. This is a new way to automatically detect prostate cancer and its genetic characteristics without the need for human supervision, which means it could possibly help in making better treatment decisions. Prostate cancer is a common cancer type in men, yet some of its traits are still under-explored. One reason for this is high molecular and morphological heterogeneity. The purpose of this study was to develop a method to gain new insights into the connection between morphological changes and underlying molecular patterns. We used artificial intelligence (AI) to analyze the morphology of seven hematoxylin and eosin (H & E)-stained prostatectomy slides from a patient with multi-focal prostate cancer. We also paired the slides with spatially resolved expression for thousands of genes obtained by a novel spatial transcriptomics (ST) technique. As both spaces are highly dimensional, we focused on dimensionality reduction before seeking associations between them. Consequently, we extracted morphological features from H & E images using an ensemble of pre-trained convolutional neural networks and proposed a workflow for dimensionality reduction. To summarize the ST data into genetic profiles, we used a previously proposed factor analysis. We found that the regions were automatically defined, outlined by unsupervised clustering, associated with independent manual annotations, in some cases, finding further relevant subdivisions. The morphological patterns were also correlated with molecular profiles and could predict the spatial variation of individual genes. This novel approach enables flexible unsupervised studies relating morphological and genetic heterogeneity using AI to be carried out.
|
|
| 5. |
- Erickson, A, et al.
(författare)
-
Spatially resolved clonal copy number alterations in benign and malignant tissue
- 2022
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 608:7922, s. 360-
-
Tidskriftsartikel (refereegranskat)abstract
- Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
|
|
| 6. |
|
|
| 7. |
- Erickson, Andrew, et al.
(författare)
-
The spatial landscape of clonal somatic mutations in benign and malignant tissue
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
|
|
| 8. |
|
|
| 9. |
- Herrmann, Inga, 1978-, et al.
(författare)
-
Markbaserad rening - design, funktion och bedömningkriterier vid tillsyn
- 2021
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Markbaserade reningsanläggningar för avloppsvatten har använts länge i Sverige och anses som en robust och driftsäker reningsmetod. Kommunerna som ansvarar för tillsynen har vid inspektionsbesök av anläggningar observerat olika brister i sådana markbaserade anläggningar, t.ex. förhöjd slamförekomst i slamavskiljare, fördelningsbrunn, spridarledningar och/eller luftningsrör, för höga vattennivåer i delar av anläggningen och/eller problem med ventilation. Dessa problem har också uppmärksammats i olika projekt. Det är dock generellt svårt att bedöma huruvida dessa brister har en negativ påverkan på reningsanläggningens funktion. Det finns ett behov av ökad kunskap om när en markbaserad anläggning fungerar eller inte och hur detta ska bedömas, både för att en anläggning inte ska dömas ut i onödan och för att en anläggning som inte fungerar tillfredsställande får rätt typ av åtgärd.I detta projekt undersöktes design-, funktions- och tillsynsprinciper för markbaserade anläggningar med hjälp av litteraturstudier och intervjuer. Syftet var att bidra till utformning av relevanta bedömningskriterier för markbaserade reningsanläggningar som kan användas vid prövning och tillsyn. Målen var att:- granska litteraturen inom markbaserad rening för att lista viktiga faktorer som påverkar funktionen,- jämföra svenska dimensioneringskriterier för slamavskiljare och infiltrationer med kriterier som används i andra länder (Norge och USA),- beskriva hur tillsyn av markbaserade anläggningar genomförs hos kommuner som är aktiva inom tillsyn,- belysa hur olika kommuner resonerar angående bedömningen av olika typer av brister (i detta mål ingår att bedöma hur allvarliga olika typer av brister är – det vill säga om bristerna kräver en uppföljning i form av föreläggande eller förbud eller om det räcker med information eller enklare uppföljning – och hur pass stor samstämmighet som finns mellan olika kommuner vid bedömning av bristers allvarlighet),- uppmärksamma svårigheter med att bedöma funktionen i markbaserade anläggningar och peka ut framtida områden som behöver vidare arbete, samt att- sammanfatta hur tillsyn bedrivs i andra länder och resonera kring vilka lärdomar som kan dras därur.
|
|
| 10. |
- Llorens-Bobadilla, Enric, et al.
(författare)
-
Solid-phase capture and profiling of open chromatin by spatial ATAC
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Current methods for epigenomic profiling are limited in the ability to obtain genome wideinformation with spatial resolution. Here we introduce spatial ATAC, a method that integratestransposase-accessible chromatin profiling in tissue sections with barcoded solid-phase captureto perform spatially resolved epigenomics. We show that spatial ATAC enables the discoveryof the regulatory programs underlying spatial gene expression during mouse organogenesis,lineage differentiation and in human pathology.
|
|
