| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Menden, MP, et al.
(author)
-
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
-
Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
|
|
| 7. |
|
|
| 8. |
- Abudurexiti, A, et al.
(author)
-
Taxonomy of the order Bunyavirales: update 2019
- 2019
-
In: Archives of virology. - : Springer Science and Business Media LLC. - 1432-8798 .- 0304-8608. ; 164:7, s. 1949-1965
-
Journal article (peer-reviewed)
|
|
| 9. |
|
|
| 10. |
- Gao, Y, et al.
(author)
-
Leisure Sedentary Behavior and Risk of Lung Cancer: A Two-Sample Mendelian Randomization Study and Mediation Analysis
- 2021
-
In: Frontiers in genetics. - : Frontiers Media SA. - 1664-8021. ; 12, s. 763626-
-
Journal article (peer-reviewed)abstract
- Leisure sedentary behavior, especially television watching, has been previously reported as associated with the risk of lung cancer in observational studies. This study aims to evaluate the causal association with two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms associated with leisure television watching, computer use, and driving were extracted from genome-wide association studies. Summary-level results of lung cancer overall and histological types were obtained from International Lung Cancer Consortium (ILCCO). In univariable MR using inverse-variance-weighted method, we observed causal effects of television watching on lung cancer [OR, 1.89, 95% confidence interval (CI), 1.41, 2.54; p = 2.33 × 10−5], and squamous cell lung cancer (OR, 2.37, 95% CI, 1.58, 3.55; p = 3.02 × 10−5), but not on lung adenocarcinoma (OR, 1.40, 95% CI, 0.94, 2.09; p = 0.100). No causal effects of computer use and driving on lung cancer were observed. Television watching significantly increased the exposure to several common risk factors of lung cancer. The associations of television watching with lung cancer and squamous cell lung cancer were compromised after adjusting for smoking quantity with multivariable MR. Our mediation analyses estimated indirect effects of television watching on lung cancer (beta, 0.31, 95% CI, 0.13, 0.52; p = 6.64 × 10−4) and squamous cell lung cancer (beta, 0.33, 95% CI, 0.14, 0.53, p = 4.76 × 10−4) mediated by smoking quantity. Our findings indicate that television watching is positively correlated with the risk of lung cancer, potentially mediated through affecting smoking quantity.
|
|
