| 1. |
- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 2. |
- Liu, Zhiyong, et al.
(författare)
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Compensating Effects Between Climate and Underlying Characteristics on Watershed Water Loss
- 2023
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Ingår i: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 128:6
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Tidskriftsartikel (refereegranskat)abstract
- Identifying climate impacts on watershed water loss (evapotranspiration) generally involves the interactions with land surface change (e.g., vegetation dynamics and anthropogenic disturbances). Here, we seek to understand the compensating effects of climate and underlying characteristics on watershed evapotranspiration. In this regard, an analytical solution was derived by using a simple water-energy partitioning framework for separating the individual contributions of climate and underlying characteristics to changes in watershed actual evapotranspiration between 1930-1970 and 1971-2008 over global 87 basins. We found that for the basins with larger increases in the total evapotranspiration, a positive underlying characteristic-related contribution is dominant, rather than the climate-related contribution. Tradeoffs (i.e., the compensating effects) between the contributions of climate and underlying characteristics to evaporative water loss were also identified in a few basins where there were relatively large changes in the underlying characteristic-related evapotranspiration but only a slight change in the total evapotranspiration. This suggests that the climate contribution in evapotranspiration may offset the effect of underlying characteristic-related changes over these basins, associated with stronger hydrological resilience under the double impacts of both climate and underlying factors. The results also indicate that the underlying characteristics exert greater contributions to the changes in the total evapotranspiration rather than the climate variation, and the underlying characteristic-related evapotranspiration variations are closely related to the changes in reservoirs and land-use types of the basins. The presented findings may provide an insightful understanding of interactions among climate, water, and underlying characteristics over global basins.
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| 3. |
- Sushko, Iurii, et al.
(författare)
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Applicability Domains for Classification Problems : Benchmarking of Distance to Models for Ames Mutagenicity Set.
- 2010
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Ingår i: Journal of chemical information and modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 50:12, s. 2094-2111
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Tidskriftsartikel (refereegranskat)abstract
- The estimation of accuracy and applicability of QSAR and QSPR models for biological and physicochemical properties represents a critical problem. The developed parameter of "distance to model" (DM) is defined as a metric of similarity between the training and test set compounds that have been subjected to QSAR/QSPR modeling. In our previous work, we demonstrated the utility and optimal performance of DM metrics that have been based on the standard deviation within an ensemble of QSAR models. The current study applies such analysis to 30 QSAR models for the Ames mutagenicity data set that were previously reported within the 2009 QSAR challenge. We demonstrate that the DMs based on an ensemble (consensus) model provide systematically better performance than other DMs. The presented approach identifies 30-60% of compounds having an accuracy of prediction similar to the interlaboratory accuracy of the Ames test, which is estimated to be 90%. Thus, the in silico predictions can be used to halve the cost of experimental measurements by providing a similar prediction accuracy. The developed model has been made publicly available at http://ochem.eu/models/1 .
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