Michel Dumontier discusses the development of fair and AI-ready knowledge graphs for explainable predictions in biomedicine. The document highlights the importance of integrating high-quality, linked data to improve treatment success rates while acknowledging challenges in reproducibility and explainability in AI models. It emphasizes the potential of neurosymbolic AI to combine logical reasoning and machine learning, thereby enhancing predictive accuracy and providing understandable explanations for predictions.

1. FAIR & AI Ready Knowledge Graphs
for Explainable Predictions
Michel Dumontier, PhD
Distinguished Professor of Data Science
Founder and Director, Institute of Data Science
Maastricht University
SeWeBMeDA :: 26-05-2024

2. @micheldumontier::KAUST-Hackathon:2023-02-07
2
Vast amounts of (largely open) data are now available

3. 3

4. 4
A common rejection module (CRM) for acute rejection across multiple organs identifies novel
therapeutics for organ transplantation
Khatri et al. JEM. (2013) 210 (11): 2205
DOI: 10.1084/jem.20122709
Main Findings:
1. CRM of 11 overexpressed genes predicted future injury to a graft
2. Mice treated with existing drugs against specific CRM genes extended graft survival
3. Retrospective EHR data analysis supports treatment prediction
Key Observations:
1. Meta-analysis offers a more reliable estimate of the direction and magnitude of the effect
2. Existing data can be used to generate and validate new hypotheses

5. significant effort is needed
to find the right data, make
sense of them, and use
them for a new purpose
5

6. Data scientists could be more productive
6

7. Surprisingly low reproducibility of landmark studies
39% (39/100) in psychology1
21% (14/67) in pharmacology2
11% (6/53) in cancer3
unsatisfactory in machine learning4
1doi:10.1038/nature.2015.17433 2doi:10.1038/nrd3439-c1 3doi:10.1038/483531a 4https://openreview.net/pdf?id=By4l2PbQ-
Most published research findings are false.
- John Ioannidis, Stanford University
PLoS Med 2005;2(8): e124.

8. 8
https://doi.org/10.1038/d41573-019-00074-z
Probability to launch
Nature Reviews Drug Discovery 18, 495-496 (2019)

9. 9
?
Do we have access to the data we need to
build good AI models?
To what extent will AI models improve the
success of developing effective treatments?
Can they provide adequate explanations?

11. high quality, linked,
machine accessible,
machine interpretable
(meta)data from
multiple sources and
data types
Trustworthy, data-
driven and knowledge-
aligned, explainable
models and predictions
Translational
Success

12. Human Machine collaboration
is crucial to our future work
13

13. Machines
need to be able to discover and reuse data
(and arguably any digital resource)
14

14. Research Directions
i) knowledge infrastructure to answer questions about what we
know and what we don’t know (but should)
ii) models to predict, explain, and justify
iii)tools to facilitate human-AI collaboration in creating,
enriching, and refining knowledge

15. Knowledge Infrastructure Explainable Predictions
Neurosymbolic AI

17. http://www.nature.com/articles/sdata201618
18

18. Making FAIR Data
Data
use ontologies +
vocabularies
Use standard
data format
Standardized
Metadata
3. Transform
2. Describe
add provenance,
license for data +
metadata
4. Publish
use standard
metadata format
use ontologies +
vocabularies
1. Collect
Persistent Data Identifier
Persistent Metadata
Identifier
Data Repository
Standardized
Metadata
Standardized
Data
Standardized
Data

19. Communities are publishing recipes
to make FAIR data

22. How do we know it’s FAIR?
• FAIR Enough is a system to
perform automated assessment
of the technical quality of the
FAIRness implementation.
• Uses a collections of metrics,
implemented as web services.
• Fast owing to parallel execution
• Keeps track of past assessments
to monitor status
• Offers search and query services
• Anybody can extend via service
based framework
• Open source and Docker
deployable
https://fair-enough.semanticscience.org

23. @micheldumontier::KAUST-
Hackathon:2023-02-07
https://lod-cloud.net/

24. • Since 2007, last updated 2014
• 30+ biomedical data sources
• 10B+ interlinked statements
• NCBI, EBI, SIB, DBCLS, NCBO, and many others
(chem2bio2rdf) produce this content
chemicals/drugs/formulations,
genomes/genes/proteins, domains
Interactions, complexes & pathways
animal models and phenotypes
Disease, genetic markers, treatments
Terminologies & publications
Belleau et al. JBI 2008. 41(5):706-716.
Callahan et al. ESWC 2013. 200-212
Linked Data for the Life
Sciences
Bio2RDF is an open source project that uses semantic web
technologies to make it easier to reuse biomedical data.
It provides Linked Data and a queryable RDF knowledge graph.

25. Biomedical Linked Data
has detailed provenance
linked to other resources
semantically typed
http(s) identifier
rich descriptions

26. An Interoperable Biomedical Knowledge Graph
diclofenac NSAID
db:category
drug-gene
association
pharmgkb:drug
CYP2C9*1
pharmgkb:haplotype

27. 28
Reproducible ML: new uses for existing drugs
Exploration: drug-target-disease networks
https://doi.org/10.7717/peerj-cs.281
https://doi.org/10.7717/peerj-cs.106
Custom Knowledge Portal: EbolaKB
https://doi.org/10.1093/database/bav049
Information Retrieval: Phenotypes of knock-out
mouse models for the targets of a selected drug

28. het.io DRKG
ROBOKOP
PheKnowLator
Integrative KGs Semantic KGs

29. Knowledge Collaboratory (for small data)
An AI-powered (NLP model or GPT) web user interface to annotate biomedical
text (NER, RE), create standard-compliant statements (BioLink model) that can be
made publicly available as author-signed nanopublications.
📝 collaboratory.semanticscience.org/annotate

30. Technology to publish assertions using RDF
Contains RDF triples to specify the assertion,
its provenance, and digital object metadata
Digitally signed by agent
TrustyURI hash to provide globally unique,
persistent, immutable, verifiable identifier and
payload

32. 33

33. Robust, Reproducible, Explainable Predictions

34. Neurosymbolic Artificial Intelligence (NAI)
NAI aims to combine symbolic reasoning methods (logic-based reasoning & rules) with
sub-symbolic methods (neural networks, deep learning) to create models with high
predictive performance and explainability.
Specifically:
● Integrates knowledge from different modalities
● Able to perform complex reasoning (e.g. deduction, induction, synthesis)
● Able to learn small and big data
● Robust to noise and nonsense
● Handle cases out of the learning distribution
● Offer explanations (e.g. causal account of the phenomenon) and justifications
(the evidence that supports the claims)

35. Predict new drug applications in a documented and
reproducible manner
36
AUC 0.90 across all therapeutic indications
Scripts not available. Feature tables
available.
Not reproducible!
Result: ROCAUC 0.83
Celebi R, Rebelo Moreira J, Hassan AA, Ayyar S, Ridder L,
Kuhn T, Dumontier M. 2020. Towards FAIR protocols and
workflows: the OpenPREDICT use case. PeerJ Computer
Science 6:e281 https://doi.org/10.7717/peerj-cs.281

36. Explainable AI
• XAI methods such as SHAP
provide information about
feature importance for the model
and in individual predictions
• When applied to OpenPredict,
it’s too complicated
understand the contributions of
derived features
• However, it is clearer when
using a single feature predictor

37. XPREDICT
Identify a set of ranked paths through the KG that offer plausible explanations for
a predicted drug indication based on their similarities to known drug-disease pairs.
1. Path generation
2. Path ranking
3. Explanation generation
@micheldumontier::KAUST-
Hackathon:2023-02-07

39. Graph Representation Learning
We want to automatically discover effective
representations needed for classification from raw data.
In graph representation learning, we encode the
topology, node attributes, and edge information into low-
dimensional vectors (or embeddings).
These vector can then be used as features to train
classifiers for link prediction, node classification, graph
classification, etc

40. GNN
Graph Neural Networks (GNNs) iteratively update node representations by
aggregating features from neighboring nodes and possibly edges.
Several methods (e.g. Saliency Maps) exist to extract a model-wise explanation for
link prediction, node/graph classification.
Graph Neural Networks

41. But I don’t find these explanations salient at all.

42. Embeddings don’t lend themselves to meaningful
explanations
because each dimension does not necessarily
represent or correspond with something we
recognize

43. Methodology
1. Use Graph Neural Networks to capture
semantics, graph structure and relationships
between nodes
2. Apply Saliency Maps on predictions made by
GNNs to identify relevant nodes for a specific
prediction; this provides valuable insights into
the graph's topology and highlights the most
important components
3. Saliency Maps assign a score to each node in
the network, which can be used to rank paths
involving genes, pathways, diseases, and
compounds

44. Experiments
Task: Link Prediction: Predict (Compound, treats, Disease)
Dataset: Drug Repurposing Knowledge Graph
Models: GraphSAGE, Graph Convolutional Network (GCN), Graph Attention
Network (GAT)
Metrics:
• Precision: ratio of true positives to predicted positives
• Recall: ratio of true positives to actual positives
• Hits@5 & Hits@10: for each test instance we predicted the tail and assessed
whether the rank of the predicted tail is below 5 or 10

45. Prediction & Explanation for:
Donepezil treats Alzheimer
The primary goal of Alzheimer's drugs,
including Donepezil, is to maintain elevated
acetylcholine (ACh) levels, thereby
compensating for the loss of functioning
cholinergic brain cells
Explanation subgraph emphasizes the crucial
role of Donepezil binding to
acetylcholinesterase (AChE) and
butyrylcholinesterase (BChE)
Slide 46 of 14

46. Summary
Finding effective drugs remains an outstanding challenge in biomedicine.
Much progress has been made in constructing semantic biomedical knowledge
graphs, and new infrastructure is available to publish, discover, and reuse
biomedical knowledge in a manner that is FAIR and de-centralized.
Embeddings-based prediction approaches show promising performance
(notwithstanding data bias), but remain difficult to explain.
Neurosymbolic systems retain the semantics of the knowledge, and show promise
in generating predictions that can recover logical explanations.

47. Michel Dumontier, PhD
Distinguished Professor of Data Science
Founder and Director, Institute of Data Science
Department of Advanced Computing Sciences
Maastricht University
michel.dumontier@maastrichtuniversity.nl
Knowledge Infrastructure
Explainable Predictions
Neurosymbolic AI
FAIR & AI
Ready
Knowledge
Graphs
for
Explainable
Predictions