This document discusses a biology research paper that uses a mouse model to understand the progression of Alzheimer's disease. It summarizes the paper's argument and evidence in four key claims: 1. Tau pathology is age-dependent in mice. 2. Human Tau is propagated synaptically in mice. 3. Mouse Tau is recruited by Human Tau to aggregate. 4. Tau pathology results in neurodegeneration accompanied by gliosis. The summary provides an overview of the paper's central argument that tau and tangles lead to neurodegeneration, as supported by data from four experimental studies using the mouse model and citations of outside experiments.

1. ModelingAlzheimer’sDiseaseReseach
Claims,Evidence,andArgumentsfroma
BiologyResearchPaper
Jodi Schneider, Novejot Sandhu
ISSA ISSA – Amsterdam – 2018-07-05

2. Theoretical Framework
• Scientific paper as an argument

3. Theoretical Framework
• Scientific paper as an argument
– “Scientific publications are documentary
representations of defeasible arguments,
supported by data and repeatable methods.”
(Clark, Ciccarese, Goble 2014).
Clark, Tim, Paolo N. Ciccarese, and Carole A. Goble. "Micropublications:
a semantic model for claims, evidence, arguments and annotations in
biomedical communications." Journal of biomedical semantics 5.1 (2014): 28.

4. Theoretical Framework
• Scientific paper as an argument
– “Scientific publications are documentary
representations of defeasible arguments,
supported by data and repeatable methods.”
(Clark, Ciccarese, Goble 2014)
• Micropublications model
Clark, Tim, Paolo N. Ciccarese, and Carole A. Goble. "Micropublications:
a semantic model for claims, evidence, arguments and annotations in
biomedical communications." Journal of biomedical semantics 5.1 (2014): 28.

5. Micropublications Model
[Clark, Ciccarese, Goble (2014) Micropublications: a semantic model for claims, evidence, arguments and
annotations in biomedical communications.]
5

6. Micropublications Model
[Clark, Ciccarese, Goble (2014) Micropublications: a semantic model for claims, evidence, arguments and
annotations in biomedical communications] 6

7. 4. Create a Micropublication
3. Identify the Reasoning
2. Annotate using http://hypothes.is
1. Identify a scientific research paper
Approach

8. Step 1: Choose Our Data

9. Uh-Oh, It’s Complex!
Neurofibrillary tangles advance from layer
II of the entorhinal cortex (EC-II) toward
limbic and association cortices as
Alzheimer’s disease evolves. However, the
mechanism involved in this hierarchical
pattern of disease progression is unknown.
We describe a transgenic mouse model ….

10. Step 2: Annotate the Article
Conclusion
What we know about
Alzheimer's
What is
hypothesize
d to be true

11. Step 3: Identify the Reasoning
• Central Argument
– Tau & tangles lead to neurodegeneration
• Support
– Data from 4 experimental studies using a
mouse model.
– Citation of outside experiments.

12. Step 4: Create a micropublication

13. Step 4: Create a micropublication
A mouse model of tau pathology is used to understand the
mechanism and progression of Alzheimer's disease (C0).
1. Tau pathology is age-dependent in mice (C1).
2. Human Tau is propagated synaptically in mice (C2).
3. Mouse Tau is recruited by Human Tau to aggregate (C3).
4. Tau pathology results in neurodegeneration which is
accompanied by gliosis (C4).

14. Experimental data supporting claim 4
Claim
Data
Methods
Materials

15. Experimental data supporting claim 4

16. Experimental data supporting claim 4
Data

17. Experimental data supporting claim 4
Claim
Data

18. Experimental data supporting claim 4
Claim
Data
Methods

19. Experimental data supporting claim 4
Claim
Data
Methods
Materials

20. Claim
Data
Methods
Materials
Citation of outside experiments
supporting claim 4

21. Claim
Data
Methods
Materials
Citation of outside experiments
supporting claim 4

22. Citation of outside experiments
supporting claim 4
• Claim 4 is supported by the
biomarker materials, which are
justified by a chain of citations
– “PSD-95, a postsynaptic marker
that has been reported to decrease
early in neurodegeneration (Zhao
et al., 2006)”.
– Zhao in turn cites Lacor et al.
2004

23. Future Work
• Mine arguments by first extracting
methods from experimental research
articles.
• First: automatically extract methods and
manually infer the knowledge claims
that the method COULD support.
• Later: characterize the types of claims
authorized by the method.

24. Applications
• Argument-based information retrieval
• Generate summaries of the argument
• Audit argument networks

27. Teufel, S. (2014). Scientific Argumentation Detection as Limited-domain Intention Recognition. In ArgNLP 2014
Frontiers and Connections between Argumentation Theory and Natural Language Processing. http://ceur-ws.org/Vol-
1341/paper14.pdf
Teufel’s model

28. Using Array tomography with two different
indicators red (post) PSD and green (pre)
synapsin I proteins to identify the densities of
pre and post synaptic structures.

29. [Clark, Ciccarese, Goble (2014) Micropublications: a semantic model for claims, evidence,
arguments and annotations in biomedical communications]

30. Mapping Scholarship

31. “[Y]ou can transform a fact into fiction or a fiction
into fact just by adding or subtracting references”
- Bruno Latour
Latour, Bruno. Science in action: How to follow scientists and engineers through society. Harvard University Press, 1987. p33

32. Funded grants with citation bias &
citation distortion.
Greenberg, Steven A. "How citation distortions create unfounded
authority: analysis of a citation network." BMJ 339 (2009): b2680.
https://doi.org/10.1136/bmj.b2680

33. Citing fake science harms people
A paper about a clinical trial for renal disease was retracted because:
“‘the trial had not been approved by the ethics committee, the involvement of
a statistician could not be verified, [and] the trial was not a double-blind study,
because Dr Nakao knew the treatment allocation’.”
“Nevertheless, the COOPERATE study was cited by 173 review articles and 58
secondary clinical studies that enrolled a total of 35,929 patients.”
“The harm done by COOPERATE is thus 4-fold:
• patients were enrolled in an experimental therapy for a condition which
already had an accepted therapy;
• time, energy and money were wasted by patients and investigators;
• false information pervaded the literature;
• and combination therapy was accepted more quickly and used more widely
than it might have been otherwise.”
Steen, R. G. (2011). Retractions in the medical literature: how many
patients are put at risk by flawed research?. Journal of Medical
Ethics, 37(11), 688-692.

34. Citing fake science harms people
A paper about a clinical trial for renal disease was retracted because:
“‘the trial had not been approved by the ethics committee, the involvement of
a statistician could not be verified, [and] the trial was not a double-blind study,
because Dr Nakao knew the treatment allocation’.”
“Nevertheless, the COOPERATE study was cited by 173 review articles and 58
secondary clinical studies that enrolled a total of 35,929 patients.”
“The harm done by COOPERATE is thus 4-fold:
• patients were enrolled in an experimental therapy for a condition which
already had an accepted therapy;
• time, energy and money were wasted by patients and investigators;
• false information pervaded the literature;
• and combination therapy was accepted more quickly and used more widely
than it might have been otherwise.”
Steen, R. G. (2011). Retractions in the medical literature: how many
patients are put at risk by flawed research?. Journal of Medical
Ethics, 37(11), 688-692.

35. Take away messages
• Biomedicine has evolved multiple approaches
for managing and appraising individual papers
and bodies of “facts”.
• Citations come in many shapes and sizes.
• Citations may support “facts” – as part of a
larger scientific fabric that includes data,
evidence, arguments.
• Powermove: identify the critical supports
(think Jenga)

36. Take away messages
• Network analysis may help identify
problematic citation practices.
• Modeling arguments can help identify the
robustness of a claimed “fact”.
• Semantic models could enable inference-
based reasoning and citation network
querying.
• Relevant citation corpora exist.