20200626-iqbio-intro.pdf

Transcript

1. Healthcare Innovation Replicathon 2020 IQ BIO REU, UPR-RP Data Sciences, Dana-Farber Cancer Institute Biostatistics, Harvard TH Chan School of Public Health Patrick Kimes, Kelly Street, Jill Lundell, Mercedeh Movassagh Luli Zou, Ana Betty Villaseñor-Altamirano
2. HEALTHCARE INNOVATION REPLICATHON 12 y 13 de julio de 2019
3. Hi! Ana Betty Patrick Jill Mercedeh Kelly Luli
4. I’d like to thank the Academy… Keegan Korthauer, PhD Alejandro Reyes, PhD for making this Patricia Ordóñez, PhD Juan S. Ramírez-Lugo, PhD Rafael Irizarry, PhD for making this possible
5. Code of Conduct https://www.pkimes.com/PR2020replicathon/code_of_conduct Assume competence in the people you interact with. There are no stupid questions. Be considerate in speech and actions, and actively seek to acknowledge and respect the boundaries of fellow community members. Take care of each other. Alert one of the organizers or facilitators if you notice a dangerous situation, someone in distress, or a potential violation of this Code of Conduct, even if it seems inconsequential. We do not tolerate harassment in any form.
6. part I. the crisis
7. http://jtleek.com/talks.html
9. “many scientific studies are difficult or impossible to replicate or reproduce.”
10. https://doi.org/10.1371/journal.pmed.0020124
11. https://doi.org/10.1371/journal.pmed.0020124 “Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true.”
12. “… replications of 100 experimental and correlational studies …” https://www.ncbi.nlm.nih.gov/pubmed/26315443
13. “39% of effects were subjectively rated to have replicated the original results.” “… replications of 100 experimental and correlational studies …” https://www.ncbi.nlm.nih.gov/pubmed/26315443
14. 39%?? https://www.ncbi.nlm.nih.gov/pubmed/26315443
15. http://jtleek.com/talks.html
16. http://jtleek.com/talks.html
17. http://jtleek.com/talks.html
18. http://jtleek.com/talks.html
19. http://jtleek.com/talks.html
20. http://jtleek.com/talks.html
21. http://jtleek.com/talks.html
22. what’s going on?
23. let’s clarify some language reproducibility replicability
24. let’s clarify some language reproducibility replicability the ability to take the original data and the computer code used to analyze the data and reproduce all of the numerical findings from the study https://simplystatistics.org/2016/08/24/replication-crisis/
25. let’s clarify some language reproducibility replicability the ability to take the original data and the computer code used to analyze the data and reproduce all of the numerical findings from the study https://simplystatistics.org/2016/08/24/replication-crisis/
26. let’s clarify some language reproducibility replicability the ability to repeat an entire study, independent of the original investigator without the use of original data https://simplystatistics.org/2016/08/24/replication-crisis/
27. let’s clarify some language reproducibility replicability the ability to repeat an entire study, independent of the original investigator without the use of original data https://simplystatistics.org/2016/08/24/replication-crisis/
28. let’s clarify some language reproducibility replicability
29. replicability
30. what’s going on? replicability
31. crisis: experiments are replicated. results not so much. replicability
32. should we expect scientific results to always replicate? replicability
33. Psychology studies reproducibility 2 https://www.nytimes.com/2015/09/01/opinion/psychology-is-not-in-crisis.html? “But the failure to replicate is not a cause for alarm; in fact, it is a normal part of how science works.”
34. https://simplystatistics.org/2016/08/24/replication-crisis/ “the replication crisis in science is largely attributable to a mismatch in our expectations of how often findings should replicate and how difficult it is to actually discover true findings in certain fields.”
35. https://simplystatistics.org/2013/08/01/the-roc-curves-of-science/ “…I argue that the rate of discoveries is higher in biomedical research than in physics. But, to achieve this higher true positive rate, biomedical research has to tolerate a higher false positive rate.”
36. should we expect scientific results to always replicate? not always replicability
37. crisis: experiments are replicated. results not so much. or maybe that’s science? replicability
38. 39%??
39. replicability crisis opportunity
40. part II. the question
41. our question https://www.ncbi.nlm.nih.gov/pubmed/22460902 https://www.ncbi.nlm.nih.gov/pubmed/22460905
42. https://www.ncbi.nlm.nih.gov/pubmed/22460902 https://www.ncbi.nlm.nih.gov/pubmed/22460905 our question
43. drug sensitivity in cancer cell lines
44. drug sensitivity in cancer cell lines what is a cell line?
45. drug sensitivity in cancer cell lines cell line cell culture from a single cell that can grow indefinitely given appropriate conditions • easily grown • relatively inexpensive • amenable to high- throughput testing https://www.ncbi.nlm.nih.gov/pubmed/26248648
46. drug sensitivity in cancer cell lines what do we mean by drug sensitivity?
47. drug sensitivity in cancer cell lines viability relative measure of cell line abundance after treatment
48. drug sensitivity in cancer cell lines dose response curve model fit to viability as a function of drug concentration
49. drug sensitivity in cancer cell lines IC50 IC50 concentration at which cell growth is inhibited 50%
50. drug sensitivity in cancer cell lines AUC area under the activity curve AUC
51. drug sensitivity in cancer cell lines got it! … but why?
52. drug sensitivity in cancer cell lines clinical https://www.ncbi.nlm.nih.gov/pubmed/26248648
53. drug sensitivity in cancer cell lines important, impactful research!
54. https://www.ncbi.nlm.nih.gov/pubmed/22460902 https://www.ncbi.nlm.nih.gov/pubmed/22460905 our question
55. https://www.ncbi.nlm.nih.gov/pubmed/24284626
56. https://www.ncbi.nlm.nih.gov/pubmed/24284626
57. https://www.ncbi.nlm.nih.gov/pubmed/27905415
59. part III. the opportunity
60. crisis: experiments are replicated. results not so much. replicability opportunity
61. what does it mean for results to “replicate”? replicability
62. what does it mean for results to “replicate”? good question!! replicability
64. crisis: experiments are replicated. results not so much. replicability opportunity
65. crisis: experiments are replicated. results not so much. or maybe yes? opportunity replicability
66. Healthcare Innovation Replicathon 2020 IQ BIO REU, UPR-RP Data Sciences, Dana-Farber Cancer Institute Biostatistics, Harvard TH Chan School of Public Health Patrick Kimes, Kelly Street, Jill Lundell, Mercedeh Movassagh Luli Zou, Ana Betty Villaseñor-Altamirano