| 1. |
- Alonso, Lorena, et al.
(författare)
-
TIGER : The gene expression regulatory variation landscape of human pancreatic islets
- 2021
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 37:2
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D.
|
|
| 2. |
- Duran-Ferrer, Marti, et al.
(författare)
-
The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome
- 2020
-
Ingår i: NATURE CANCER. - : Springer Nature. - 2662-1347. ; 1:11, s. 1066-1081
-
Tidskriftsartikel (refereegranskat)abstract
- We report a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. Differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive individual-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. We construct a DNA-methylation-based mitotic clock, called epiCMIT, whose lapse magnitude represents a strong independent prognostic variable in B-cell tumors and is associated with particular driver genetic alterations. Our findings reveal DNA methylation as a holistic tracer of B-cell tumor developmental history, with implications in differential diagnosis and the prediction of clinical outcome. Martin-Subero and colleagues analyze DNA methylation patterns in B-cell tumors and their normal cells of origin, and develop epiCMIT, a methylation-based mitotic clock with prognostic relevance.
|
|
| 3. |
- Puiggròs, Montserrat, et al.
(författare)
-
Automatic characterization of ornamentation from bassoon recordings for expressive synthesis
- 2006
-
Ingår i: 9th International Conference on Music Perception & Cognition. - Bologna : Bonomia University Press. - 8873951554 ; , s. 1533-1538
-
Konferensbidrag (refereegranskat)abstract
- Expressive performance characterization is traditionally based on the analysis of the main differences between performances, players, playing styles and emotional intentions. This work addresses the characterization of expressive bassoon ornaments by analyzing audio recordings played by a professional bassoonist. This characterization is then used to generate expressive ornaments from symbolic representations by means of Machine Learning
|
|
