The document discusses the use of natural language processing (NLP) in digital disease informatics, highlighting its potential to convert unstructured health data into structured formats. It presents various case studies, including global infectious disease alerting and phenotype extraction, to demonstrate the effectiveness of NLP techniques in operational settings. Challenges such as data multilinguality and real-time scaling are also addressed, with an emphasis on the importance of robust data collection from diverse health-related text sources.

1. Exploiting NLP for Digital Disease Informatics
University of Warwick, October 15th 2015
Nigel Collier, Language Technology Lab
Department of Theoretical and Applied Linguistics

2. Really understanding natural language is the next grand
challenge
• High throughput methods have transformed biomedicine into a
data-rich science
• All genes in a genome, all proteins in a proteome, all transcripts in a
cell, all metabolic processes in a tissue…

3. Really understanding natural language is the next grand
challenge
• High throughput methods have transformed biomedicine into a
data-rich science
• All genes in a genome, all proteins in a proteome, all transcripts in a
cell, all metabolic processes in a tissue…
• A significant portion of human health data is ‘messy data’
existing only as unstructured text
• Biomedical literature, Clinical trials data, Lab notebooks, Clinical
records, Diagnostic reports, News reports, Social media messages
• Represents the most contextually grounded, high precision
information about an individual’s health, attitudes and behaviours

4. Really understanding natural language is the next grand
challenge
• High throughput methods have transformed biomedicine into a
data-rich science
• All genes in a genome, all proteins in a proteome, all transcripts in a
cell, all metabolic processes in a tissue…
• A significant portion of human health data is ‘messy data’
existing only as unstructured text
• Biomedical literature, Clinical trials data, Lab notebooks, Clinical
records, Diagnostic reports, News reports, Social media messages
• Represents the most contextually grounded, high precision
information about an individual’s health, attitudes and behaviours
• Natural language processing (NLP) is a cornerstone
technology to translate ‘messy data’ into structured forms that
are systematically encoded, e.g. SNOMED-CT, ICD.

5. Experience from personal research
(1) Global infectious disease alerting and
mapping
(2) Extracting a database of phenotype terms
(3) Understanding the voice of the patient
(4) Chemical cancer risk assessment
(5) Critical hypothesis generation from literature

6. Typical workflow from text to knowledge
raw text
document
sentence
segmentation
tokenization
lexical
featurisation
entity
recognition
trigger
detection
relation
extraction
event
extraction
entity
grounding
knowledge objects
syntactic
parsing

7. Broad Research Objectives
• Extrinsic: Robust data collection from across health-related text types:
literature, patient records, news, social media (public health alerts, developing
disease profiles, etc.)
• Intrinsic: Understand how NLP/ML/Ontology techniques perform and can be
improved in operational settings

8. BIOCASTER: GLOBAL INFECTIOUS DISEASE
ALERTING AND MAPPING
Case study #1
[5] Collier, N. et al. (2008). BioCaster: detecting public health rumors with a Web-based text mining system. Bioinformatics, 24(24), 2940-2941.
[6] Collier, N., et al. (2011). OMG U got flu? Analysis of shared health messages for bio-surveillance. J. Biomedical Semantics, 2(S-5), S9.
[7] Hay, S. I., et al. (2013). Global mapping of infectious disease. Philosophical Transactions of the Royal Society of London B: Biological
Sciences, 368(1614), 20120250.

9. Infectious diseases spread rapidly
“We live in a world where threats to health arise from the speed and volume of air
travel, the way we produce and trade food, the way we use and misuse antibiotics,
and the way we manage the environment…”
- Dr. Margaret Chan, DG WHO
SARS, 2003
HK, world
H5N1 flu, 2003-
PRC, Thailand,
ROC, Vietnam
Foot & mouth, 2001
United Kingdom
Ebola, 2014-
Guinea, Liberia,
Sierra Leone,
Nigeria

10. Trend graphs
Event summaries
Event alerts
Ontology browsing
Email/GeoRSS alerting
Watchboard, etc.
Real time Twitter
analysis
Up to date news in
12 languages
Event database search
GHSI
partners
US
UK
FR
DE
WHO
IT
JP
CA
Digital epidemic surveillance with BioCaster

11. Example frame
<SLOT name="HAS_DISEASE" type="DISEASE" content="Anthrax" alt="" root_term="Anthrax" bid=""/>
<SLOT name="HAS_LOCATION.COUNTRY" type="LOCATION" content="Morocco" alt="" root_term="Morocco" bid=""/>
<SLOT name="HAS_LOCATION.PROVINCE" type="LOCATION" content="Marrakech" alt="" root_term="" bid=""/>
<SLOT name="HAS_AGENT" type="micro_organism" content="Bacillus anthracis" alt="" root_term="" bid=""/>
<SLOT name="HAS_SPECIES" type="animal" content="human" alt="" root_term="" bid=""/>
<SLOT name="TIME.relative" type="string" content=""/>
<SLOT name="INTERNATIONAL_TRAVEL" type="Boolean" content="false"/>
<SLOT name="DELIBERATE_RELEASE" type="Boolean" content="false"/>
<SLOT name="ZOONOSIS" type="Boolean" content="false"/>
<SLOT name="DRUG_RESISTANCE" type="Boolean" content="false"/>
<SLOT name="FOOD_CONTAMINATION" type="Boolean" content="false"/>
<SLOT name="HOSPITAL_WORKER" type="Boolean" content="false"/>
<SLOT name="FARM_WORKER" type="Boolean" content="false"/>
<SLOT name="MALFORMED_PRODUCT" type="Boolean" content="false"/>
<SLOT name="NEW_TYPE_AGENT" type="Boolean" content="false"/>
<SLOT name="SERVICE_DISRUPTION" type="Boolean" content="false"/>
<SLOT name="CATEGORY_A" type="Boolean" content="true">
</EVENT>

12. Technical challenges
X0,000 news providers
REAL TIME
SCALING 30,000-40,000 news items/day
900 on topic/day
200 events/day
4 alerts/day

13. Technical challenges
X0,000 news providers
MULTILINGUALITY
Avian Flu
Influenza aviaire
鳥インフルエンザ
조류인플루엔자
โรคไข้หวัดนก
Cúm gia cầm
REAL TIME
SCALING
 Increased sensitivity and
timeliness from multilingual
news
News event counts for porcine foot-
and-mouth outbreak in South Korea
2010-2011

14. Technical challenges
X0,000 news providers
MULTILINGUALITY
REAL TIME
SCALING
AMBIGUITY
“Obama fever builds as Americans
await a new era”
Equine influenza in Camden
Camden (UK) Camden (AU) Camden (CA) + 19 others
Entity identification
Toponym grounding
Tajoura Tajura Tajoora…
Variant transliterations
Coreference
“Two British holidaymakers fell ill… ”
“Two male pensioners died…”
2 or 4 victims?
Temporal identification
“The Spanish flu outbreak…

15. Semantic pipeline

16. Source: BioCaster
Outbreak characteristics: Early surge vs multi-modal transmission
News event frequency over time
Looking for bursts of activity

17. Source: GENI-DB
0
1
0
40
80
120
160
200
ct
μ
μ+3σ
Gold
Alerts with the C2 test statistic:
St = max(0, (Ct – (μt + 3σt))/ σt)
First English language
reports (MMWR + AP)
Understanding norms and their violations

18. 5 detection algorithms
1. Early aberration reporting system (EARS) C2 algorithm
• captures the number of standard deviations that the current count exceeds the history mean;
• St = max(0, (Ct – (μt + kσt))/ σt)
2. EARS C3 algorithm
• similar to C2 except that C3 uses a weighted sum of the previous 3 days for the current period;
3. W2 algorithm
• a modified version of C2 which ignores history counts on Saturdays and Sundays to compensate for day of week effects;
4. F statistic
• compares the variance in the history window to the variance in the current window;
• St = σt
2 +σb
2
5. Exponential Weighted Moving Average (EWMA)
• provides less weight to days in the history that are further from the test day.
• St = (Yt – μt)/[σt * (λ/(2- λ))1/2], where Y1 = C1 and Yt = λCt + (1- λ)Yt-1
Model parameters were estimated based on an additional 5 epidemic data sets from ProMED-mail (data not
shown)
[8] Burkom H. S. (2005), “Accessible Alerting Algorithms for Biosurveillance”. National Syndromic Surveillance Conference
[9] Jackson M. L. et all (2007), “A simulation study comparing aberration detection algorithms for syndromic surveillance” Medical Informatics and Decision
Making , 7(6): BMC, DOI: 10.1186/1472-6947-7-6.
[10] Madoff L. (2004), “ProMED-mail: An early warning system for emerging diseases”. Clin Infect Dis , 39(2): 227–232.

19. # Disease Country ProMED-alerts
1 Hand,foot,mo
uth
PR China 9
2 Ebola Congo 17
3 Yellow fever Brazil 28
4 Influenza USA 21
5 Cholera Iraq 5
6 Chikungunya Singapore 8
7 Anthrax USA 15
8 Yellow fever Argentina 5
9 Ebola Reston Philippine
s
15
# Disease Country ProMED-alerts
10 Influenza Egypt 49
11 Plague USA 8
12 Dengue Brazil 27
13 Dengue Indonesia 14
14 Measles UK 13
15 Chikunguny
a
Malaysia 15
16 Yellow fever Senegal 0
17 Influenza Indonesia 35
18 Influenza Banglade
sh
3
14 countries and 11 infectious disease types. 366 days of news data was collected from BioCaster for each disease and
country. The study period is 17th June 2008 to 17th June 2009
Creating a benchmark data set

20. C3 C2 W2 F-statistic EWMA
Sensitivity 0.74 0.66 0.66 0.78 0.73
(0.69-0.78) (0.61-0.72) (0.60-0.71) (0.74-0.82) (0.68-0.78)
Specificity 0.96 0.98 0.98 0.92 0.95
(0.95-0.96) (0.98-0.98) (0.98-0.99) (0.91-0.92) (0.94-0.96)
PPV 0.55 0.64 0.65 0.46 0.47
(0.98-0.99) (0.98-0.99) (0.98-0.99) (0.98-0.99) (0.98-0.99)
NPV 0.98 0.98 0.98 0.98 0.98
(0.98-0.99) (0.98-0.99) (0.98-0.99) (0.98-0.98) (0.98-0.99)
Alarms/100 days 6.48 4.52 4.17 12.34 7.85
F-measure 0.63 0.65 0.66 0.58 0.58
Results in parentheses show 95% confidence intervals
[11] Collier, N. (2009), “What’s unusual in online disease outbreak news?”, in BMC Biiomedical Semantics, 1(2).
Comparison of 5 aberration detection algorithms

21. Field evaluation
• (2006-2012) Global Health Security Initiative– a unique initiative by G7+WHO+EC to
bring together end-users, system providers and stakeholders to test the feasibility of
open source public health intelligence systems.
[12] Barboza, P., Vaillant, L., Le Strat, Y., Hartley, D. M., Nelson, N. P., Mawudeku, A., Madoff, L. C., Linge, J. P., Collier, N., Brownstein, J. S. and Astagneau,
P. (2014). Factors Influencing Performance of Internet-Based Biosurveillance Systems Used in Epidemic Intelligence for Early Detection of Infectious Diseases
Outbreaks. PloS one, 9(3), e90536.
[13] Barboza, P., Vaillant, L., Mawudeku, A., Nelson, N., Hartley, D., Madoff, L., Linge, J., Collier, N., Brownstein, J., Yangarber, R. and Astagneau, P. (2013),
“Evaluation of epidemic intelligence systems integrated in the Early Alerting and Reporting project for the detection of A/H5N1 Influenza events”, PLoS One,
8(3):e57252.
Major findings for A/H5H1:
- Detection rates for individual systems from
31% to 38%
- Rising to 72% for the combined system
- PPV ranged from 3% to 24%
- F1 ranged from 6% to 27%
- Sensitivity ranged from 38% to 72%
- Average improvement in alerting over WHO or
OIE was 10.2 days

22. User outcomes
• Used by WHO and Japanese MoH to detect early cases during
the A(H1N1) pandemic;
• Used by ECDC to monitor diseases during the Shanghai Expo
2010, London Olympics 2012;
• Used by French Institute for Public Health to monitor for human-
to-human A(H5N1) transmission;
• Used by GHSI members to monitor for suspected accidental or
deliberate releases;
• Used by CDC to help monitor for health impact of the Oil spill in
the Gulf of Mexico;

23. PHENOMINER/PHENEBANK: EXTRACTING A
DATABASE OF PHENOTYPE TERMS
Case study #2
[14] Collier, N., Groza, T., Smedley, D., Robinson, P., Oellrich, A. and Rebholz-Schuhmann, D. (2015). PhenoMiner: from text to a database of
phenotypes associated with OMIM diseases. Database, Oxford University Press (in press).
[15] Collier, N., Oellrich, A. and Groza, T. (2013), “Toward knowledge support for analysis and interpretation of complex traits”, Genome Biology
14(9):214.

24. What is a phenotype?
Image courtesy of Washington, Haendel, Mungall, Ashburner, Westfield and Lewis (2009), “Linking human diseases
to animal models using ontology-based phenotype annotation”, PLoS Biology, 7(11):e1000247.

25. “… patients were selected for FOXP2 screening only if
they fulfilled the following criteria: presence of
speech articulation problems diagnosed by a clinician …”
HPO: 0009088 Speech articulation difficulties
Image courtesy of Damian Smedley,
Welcome Trust Sanger Institute,
Hinxton and Tudor Groza, University
of Queensland, Brisbane
Coding personal terminology

26. SVM learn-to-rank (pairwise)
Maximum entropy
Priority list heuristic
“… patients were selected for FOXP2 screening only if
they fulfilled the following criteria: presence of
speech articulation problems diagnosed by a clinician”
“… patients were selected for FOXP2 screening only if
they fulfilled the following criteria: presence of
speech articulation problems diagnosed by a clinician”

27. Creating a benchmark data set
• Data from OMIM cited autoimmune literature (112 abstracts, 472
phenotypes, 1611 gene/gene products).

28. F-scores computed using ablation on various domain
ontologies

29. F-scores using 3 hypothesis resolution strategies
[16] Collier, N., Tran, M., Le, H. Ha, Q., Oellrich, A. Rebholz-Schuhmann, D. (2013), “Learning to recognize phenotype candidates in the auto-immune literature
using SVM re-ranking”, PLoS One 8(10): e72965.

30. Lesson learnt … sampling matters
Resource Size (records)
PubMed 23,765,575
GENIA 2,000
PennBioIe 1414
FSU-PRGE 3,236
Arizona corpus 2,775
sentences
I2B2/VA 2010 826

31. M1: In domain approach
Sample B1
Learner
Knowledge
Evaluation (A)
Sample B2
Sample B

32. M2: Out domain approach
Sample A
Learner
Knowledge
Evaluation (B)
Sample B

33. M3: Mix-in approach
Sample A
Learner
Knowledge
Evaluation (B)
Sample BSample B
+

34. M4: stack approach
Learner
Knowledge
Evaluation (B)
Sample BSample B
Sample A
Learner
Knowledge

35. M5: binary class
Sample A
Learner
Knowledge
Evaluation (B)
Sample B
Sample B
+
Re-label PHE
PHE-1 and PHE-2
Re-label PHE-1
and PHE-2 as PHE

36. M6: frustratingly simple
Sample A
Learner
Knowledge
Evaluation (B)
Sample B
Sample B
+
Re-label features as
Sample A, Sample B and Joint

37. 37
Near domain transfer results

38. How can we do domain adaptation better (with less
annotations)?
[17] Collier, N., Paster, F., Campus, H., & Tran, A. M. V. (2014), “The impact of near domain transfer on biomedical named entity recognition”, Proc. 5th
International Workshop on Health Text Mining and Information Analysis (LOUHI) at the European Conference on Computational Linguistics (EACL),
Gothenburg, Sweden, pp. 11-20.

39. SIPHS: UNDERSTANDING THE VOICE OF THE
PATIENT
Case study #3
[18] Limsopatham, N. and Collier, N. (2015), “Adapting phrase-based machine translation to normalise medical terms in social media messages”,
in Proceedings of the 2015 Conference on Empirical Methods in Natural Language Processing, Lisbon, Portugal, 17-21 September 2015, pp.
1675-1680.
[19] Limsopatham, N. and Collier, N. (2015), “Towards the semantic interpretation of personal health messages from social media”, in Proceedings
of the 24th ACM International Conference on Information and Knowledge Management (CIKM 2015), Workshop on Understanding the City with
Urban Informatics (UCUI 2015), Melbourne, Australia, 19-23 October 2015.

40. What do people talk about?
Types Tweet samples
Influenza
confirmation
I got flu n coughed a lot. Now my voice is like
monster’s voice. Rrr
Influenza symptoms My day: flu-like symptoms (headache, body aches,
cough, chills, 100.9 fever). Swine flu not ruled out.
#H1N1
Flu shots I’m still getting flu shots, nothing is worth flu turning
into bronchitis into pneumonia
Self protection Cover your mouth if coughing, use a tissue, wash
your hands often & get a flu shot - protect and
defend your community from #H1N1
Medication Wondering why I didn’t take the flu shot, laying in
bed with cough drops, medicine, and the remote

41. Tracking anxiety indicators have moderate-strong correlation
with CDC seasonal flu tracking
Category Spearman’s
Rho
P-value
A 0.66 0.020
S 0.66 0.021
I 0.58 0.048
P 0.67 0.017
A+I+P 0.68 0.008
A+I+P+S 0.67 0.017
0
50
100
150
200
250
300
350
400
450
0
500
1000
1500
2000
2500
3000
46 47 48 49 50 51 52 1 2 3 4 5
CDC
A
S
I
P
A+I+P
A+I+P+S
Data source: CDC (2009-2010 flu season)
“Cover your mouth if coughing,
use a tissue, wash your hands often & get
a flu shot - protect and defend your
community”
“I’m still getting flu shots, nothing is worth
flu turning into bronchitis into pneumonia”
“I can ignore this sore throat no longer.
And, um, maybe I should have gotten
that H1N1 vaccine.“

42. Frustratingly simple models work better
Classifying respiratory syndrome: Turning 225,000 Tweets into a
high correlation influenza tracker
[22] Doan, S., Ohno-Machado, L. and Collier, N. (2012), "Enhancing Twitter data analysis with simple semantic filtering: example in tracking Influenza-Like Illnesses", in
the 2nd IEEE Conference on Healthcare Informatics, Imaging and Systems Biology: Analyzing Big Data for Healthcare and Biomedical Sciences, California, USA,
September 27-28.

43. Coding the voice of the patient in SIPHS
• Integrate the language of Social Media and Lifescience Ontologies
• ‘Voice of the patient’ – real time public health mapping/risk analysis
• Code patient-centred vocabulary and links
• Generate public health summaries, e.g. infectious diseases, ADRs
Twitter message SNOMED
preferred
term
SNOMED ID
No way I’m getting any sleep 2nite Insomnia 193462001
Take _DRUG_ and can’t even
focus forreal
Unable to
concentrate
60032008
_DRUG_ makes u skinny Weight loss 89362005

44. “You shall know a word by the company it keeps”
– (Firth, J. R. 1957)
• Existing work [1,2] used word vector similarity to measure the
semantic similarity between texts
 Performance seems depended on the used vector representation (e.g.
CBOW [1], GloVe [2])
[23] Mikolov et al. Distributed representations of words and phrases and their compositionality. NIPS 2013
[24] Pennington et al. GloVe: Global vectors for word representation. EMNLP 2014
• Recent advances in deep learning
technology [1,2] allowed the learned
representation of terms (i.e. DWRs) that
could capture the semantic similarity of
terms based on their co-occurrences e.g.
Continuous bag-of-words (CBOW) [1], Global
Vector (GloVe) [2]
44

45. Related work – Phrase-based MT
• Phrase-based MT [3]: Translate between languages by learning local
term dependencies from parallel corpora
 We adapt phrase-based MT to translate from social media language to
formal medical language
Can’t even focus forreal  no concentrate  ???
[25] Koehn et al. Statistical phrase-based translation. NAACL 2003
45

46. Adapting Phrase-based MT for Twitter Normalisation
• We use phrase-based MT to translate social media text to formal
medical text, then map the translated symptoms to a SNOMED-CT
concept
Can’t even focus forreal  unable to focus  unable to concentrate
(ID 60032008)
translate
find semantic distance
[18] Limsopatham, N. and Collier, N. (2015), “Adapting phrase-based machine translation to noramlise medical terms
in social media messages”, in Proceedings of the 2015 Conference on Empirical Methods in Natural Language Processing,
Lisbon, Portugal, September, pp. 1675-1680.

47. A Twitter Phrase
Training pairs of
Twitter phrases and
SNOMED-CT terms
A Phrase-based MT
Model
Our Mapping
Approach (i.e. Sim,
rSim)
A ranking of
mapped
concepts
e.g. ‘No way I’m getting
any sleep 2nite’
e.g.
‘no sleep week’ = ‘Insomnia’,
‘so unfocussed!!!’ = ‘Unable to
concentrate’
Using a phrase-based
model, such as Koehn et
al. (2003)
e.g.
1. Insomnia (193462001)
2. Productivity at work
(224403006)
System Architecture

48. Experimental Setup
• Instantiations of our approach:
 Sim(1): using only the best translation
 Sim(5): using the top 5 translations
 rSim(5): using the top 5 translations
• Baseline: Cosine similarity of vector representations of the original
tweet and the description of a concept
 One-hot
 Continuous Bags of Words (CBOW)
 Global Vector (GloVe)
48

49. Experimental Results
• RQ1: Does our approach perform better than SOTA DWR baselines?
0.1675
0.2232
0.2491
0.2458
0.1896
0.1869
0
0.05
0.1
0.15
0.2
0.25
0.3
Baseline Sim(1) Sim(5) rSim(5)
One-hot CBOW GloVe
Yes, all instances of our approach
markedly outperformed the DWR
baselines by up to 33%MRR-5
49
Twitter message: “unable to sleep at all”
Baseline:
Mapping: “unable to sleep at all”  ‘unable to concentrate’
Our approach:
Translation: “unable to sleep at all”  “insomnia of”
Mapping: “insomnia of”  ‘insomnia’

50. Experimental Results
• RQ2: Which types of DWRs are effective for our approach?
0.1675
0.2232
0.2491
0.2458
0.1896
0.2070
0.2104
0.2109
0.1869
0.2500
0.2638
0.2617
0
0.05
0.1
0.15
0.2
0.25
0.3
Baseline Sim(1) Sim(5) rSim(5)
One-hot CBOW GloVe
Both Sim and rSim outperform
the baseline, regardless of the
used vector representation
MRR-5

51. Experimental Results
• RQ3: Would the performance improve if we consider both original and
translated text when mapping a concept? Performances improved
when using one-hot
representationMRR-5
0.2232
0.242
0.2491
0.2556
0.2458
0.2594
0.2070
0.1953
0.2104
0.2144
0.2109
0.207
0.2500
0.2532
0.2638
0.2600
0.2617
0.2509
0.15
0.17
0.19
0.21
0.23
0.25
0.27
Sim(1) Sim(1)+ Sim(5) Sim(5)+ rSim(5) rSim(5)+
One-hot CBOW GloVe
51

52. Summary
• How we exploit the base of medical evidence is changing as access to unstructured
‘messy’ data opens up new opportunities
• Data access, bias and standards
• We can expect impact in epidemic detection, pharmacovigilence, translational health,
disease mapping, risk communication, rare disease profiling and many other areas.
• Encoding the data increases value through data mining, exchange and integration
• Machine learning outperforms dictionaries and hand built rules
• Finding the right lexical representation and right target form is key

53. Thank you
Contributions by:
Nigel Collier
nhc30@cam.ac.uk
Anna Korhonen
alk23@cam.ac.uk
Nut Limsopatham
nl347@cam.ac.uk
Further information at the
Language Technology Lab
http://ltl.mml.cam.ac.uk/
Funding: