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Mental Functioning Ontologyfor interdisciplinary research
into mental disease, emotions and drugs
Janna Hastings1,2
(ChEBI, MF and the Emotion Ontology)
1 Cheminformatics and Metabolism, European Bioinformatics Institute, UK
2 Swiss Center for Affective Sciences, University of Geneva, Switzerland
NIF Webinar, 24 April 2012
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Oxytocin is believed to play a role in various behaviors, including orgasm, social recognition, pair bonding, anxiety … it is sometimes referred to as the "love hormone".
The inability to secrete oxytocin and feel empathy is linked to sociopathy, psychopathy, narcissism and general manipulativeness.
I want…
I think…
Why mental functioning?
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Many chemicals can affect mental functioning
3
The Chemical Ontology
How does mental functioning actually work?
Biology
Neuroscience
Chemistry
Psychology
Psychiatry
Cognitive ScienceHuman
Mouse
fMRI
Gene expression
analysis
Self-reportsMetabolic analysis
Genetic profiling
EEG
Questionnaires
PET
Theories of mental functioning have testable implications for researchinto mental disease
Abducted! Replaced!
Capgras delusion: a disorder in which a person holds a delusion that a friend, spouse, parent, or other close family member has been replaced by an identical-looking impostor.
Faulty perception? Normal perception, faulty reasoning? Faulty emotional reaction to perception? Overactive imagination?
TESTABLE IMPLICATIONS
Existing vocabulariesdon’t include
computable definitions
Mental Functioning Ontology (MF)
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Modules under development: Mental diseases and emotions
BFO
MFOGMS
MD
MFO-EM
Domain-neutral ontological upper level
Mental FunctioningOntology
Ontology for GeneralMedical Science
Emotion Ontology
Mental Disease Ontology(Current focus on affective disorders and addiction)
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Motivation and Goals
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Bio-ontologies facilitate interdisciplinary scientific research
1. Standardised vocabulary with definitions and synonyms for unified database annotations
2. Hierarchical organisation for aggregation and multi-level comparison of results
3. Community adoption for comparison of results to other project results worldwide
4. Explicit relationships and underlying logic for automated reasoning to related entities
5. Explicit bridging relationships between different ontologies for exploring underlying mechanisms
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Modern scientific research relies on computational support
Data
Data
Data
Synthesis
Analysis
Reporting
Publication
Patient histories, EHR
Questionnairesand self-reports
Genomic and metabolomic
profiles
Caregiver, pscyhiatric reports
Brain scans …
For each question:
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Ontology for standardisation
MD:0000901substance abuse
MD:0000902marijuana abuse
S:09090909marijuana
---------------------------Synonym: cannabis
Synonym: THCSynonym: dronabinol
is abuse of substance
Semantics-free unique identifiers that are stable and maintainedCODE (MD) indicates WHICH ONTOLOGY A numeric identifier is unique per term
is a
Unambiguous preferred label together with a textual definition guide the annotationof this ontology term to associated data
Synonyms and other metadata are collectedto facilitate searching, disambiguation and text processing
Synonyms may be in several languagesor reflect differing naming practices in differentdisciplines
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Ontology annotations are generic across multiple databases
ID Patient Finding type Detail
1111 Smith, John MF:0000902 (marijuana abuse)
Occasional
1111 Smith, John MF:0000903 (alcohol abuse)
Occasional
1111 Smith, John MF:0000904 (nicotine abuse)
Frequent
Sample ID Sample type Conditions Genotype
1111 Illumina Golden Gate MF:0000903; MF:0000902 …
Same IDs
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Population-wide science depends on aggregation of data
Are there genes significantly enriched in all people who suffer from some addiction?
Are there differences between those people who suffer from substance addiction compared to those who suffer from process addictions?
Are there differences between those people who suffer from opiate substance addictions and those who suffer from addictions to benzodiazepines?
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Ontology for hierarchical organisationMD:0000046
addiction
MD:0000053process addiction
MD:0000053substance addiction
MD:0000054gambling addiction
MD:0000055sex addiction
MD:0000064internet addiction
MD:0000066benzodiazepine addiction
MD:0000065opiate addiction
MD:0000067diazepam addiction
MD:0000059heroin addiction
MD:0000068morphine addiction
Every ‘sex addiction’ is a ‘process addiction’, every ‘process addiction’ is an ‘addiction’Every ‘heroin addiction’ is an ‘opiate addiction’, every ‘opiate addiction’ is a ‘substance addiction’, every ‘substance addiction’ is an ‘addiction’. And so on.
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Research involves comparison of results to existing data arising from other projects, stored in public databases
A researcher obtains brain scans for several addicted patients. In order to determine how they compare to existing scans of other addicted patients and to non-addicted patients, (s)he looks in public databases.
Relating to addiction, manual examination of the BrainMap database searchcriteria suggests two patient diagnosis categories that may be relevant: alcoholism and pathological gambling
… as well as many unstructured keywords
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To amass the correct search criteria to find the data for each comparison requires careful manual examination… and that’s only one database out of hundreds
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A shared community ontology for annotation allows unified searching across databases (e.g. GOA)
BrainMap
Brede
fMRI Data Center
RIKEN Neuroimaging
Platform
NeuroSynthOpenfMRI
Nifti
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Computers can’t “see” implicit relationships between entities
Substance addiction is characterised by symptoms such as preoccupation with substance and repeated failed attempts to control the use of the substance. These are non-canonical thinking and planning activities. But, there is no easy way to automatically compare with data from other conditions that have similar symptoms.
Patient data – addicted patients
Patient data – impaired rational control of actions
or planning
Patient data – preoccupation or other compulsive
thinking? ?
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Ontologies capture explicit computable relationships between entities
MD:0000053substance addiction
MD:0001053substance addiction
disease course
realized in
MD:0001001non-canonical (impaired)
planning process
MD:0001011failed attempts to
stop substance use
has part
MD:0001002non-canonical (impaired)
thinking process
MD:0001012preoccupation with
substance use
Relationshipsare namedand have definitions
They are usedfor automated reasoning andquestion answering
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Related entities are themselves used in annotations
Patient data on symptom
assessment (Addiction) MD:0001001
non-canonical (impaired) planning process
MD:0001002non-canonical (impaired)
thinking process Patient data on symptom
assessment (Dysexecutive
syndrome)
… which allows patient data from disparate diseases (and research into
normal functioning) to be compared
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Different domains operate at different levels of granularity and focus
PATHWAYS, biological processes
METABOLIC DATA (e.g. NMR)
GENE EXPRESSION
DATA
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NMR data for metabolites of cocaineis found in
metabolomics databases -- indexed
by small molecules
Urine samples of addicted patients reveal metabolites
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Ontology relationships can explicitly bridge across different ontologies at different levels
MD:0000071cocaine addiction MD:0010071
cocaine addictiondisease course
realized in
MD:0020071use of cocaine
has part
S:00100100portion of cocaine
has input
CHEBI:27958cocaine
has granular part
Chemical and metabolic data
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Current status and ongoing work in the Emotion Ontology
BFO:Entity
BFO:Continuant BFO:Occurrent
BFO:ProcessBFO:Independent
Continuant
BFOMFO
BFO:Dependent Continuant
Cognitive Representation
Affective Representation
Mental Process
Bodily ProcessBFO:Disposition
MFO-EM
Emotion Occurrent
Organism
Emotional Action Tendencies
Appraisal
Subjective Emotional Feeling
Physiological Response to
Emotion Process
inheres_in
is_output_of
Emotional Behavioural Process
Appraisal Process
has_part
agent_of
The Emotion Ontology (MFO-EM)
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Types of emotion
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To define the characteristics of different emotions start with canonical emotions
Emotion types (such as fear) show enormous variance across instancesJust as do anatomical types, e.g. human bodies
Ontology expresses what is always true… But also aims to say something useful for representation of domain knowledge.
Solution: encode such knowledge in ‘canonical’ types
canonical fear
appraisal process
Appraisal of dangerousness
Has part Has output
Canonical fear results from an appraisal of dangerousness
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Canonical fear
canonical fear
fear
EMOTION COMPONENT CHARACTERISTIC FOR FEARAction tendency Fight-or-flightSubjective emotional feeling Negative, tense, powerlessBehavioural response Characteristic fearful facial
expressionCharacteristic appraisal Something is dangerous to me
subtype
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Canonical and non-canonical fear
Canonical fear gives rise to action tendencies that are conformant to the perceived danger
Phobia = disposition giving rise to non-canonical fear
laridaphobia : intense fear of seagulls
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Types of appraisal
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Types of subjective feelings
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Types of physiological responses
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Types of emotional behaviour
Annotation of data from Cognitive Neuroscience of Emotion
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Study Task Annotation class in MFO/MFOEM
Recognition of gender in emotional facial expressions
Visual perception of emotional facial expressions (subClassOf perception)
Recall of personal emotional memories with instructions to try re-create feeling
Memory of emotional episodes (subClassOf memory)
Listening to emotional sounds (e.g. grunts of disgust)
Auditory perception of emotional stimuli (subClassOf perception)
Viewing emotional film extracts Visual and auditory perception of emotional stimuli (subClassOf perception)
The link from perception of emotional fear in facial expressions to canonical fear is subject to empirical research
(Part of) the biochemical basis of emotion is in ChEBI
Emotions are effected in part by neurotransmitters such as dopamine, tryptophan
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dopamine(CHEBI:25375)
molecular entity (CHEBI:25375)
biological role (CHEBI:24432)
neurotransmitter(CHEBI:25512)
has role
neurotransmitter receptor activity
(GO:0030594)
Molecular function (GO:0003674)
realized in
happiness(MFOEM:42)
part of
emotion(MFOEM:1)
subtype
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Biological processes in affective disorders
Some mental diseases involve altered emotional functioning. (E.g. depression, bipolar disorder)
emotion
non-canonical sadness
ProcessDisposition
depression
mental disease
realized in
down-regulation of dopaminergic
system (GO:0032227)
has part
biological processMechanism of
action: complex
disturbances in underlying
systems
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Availability, ContactsMental Functioning Ontology available at:http://mental-functioning-ontology.googlecode.com/svn/trunk/ontology/MF.owl
Emotion Ontology available at: http://emotion-ontology.googlecode.com/svn/trunk/ontology/MFOEM.owl
Discussion mailing lists:[email protected]@googlegroups.com
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Acknowledgements Thanks!
Buffalo OntologistsBarry Smith, Werner Ceusters, Mark Jensen
Emotion Researchers in GenevaKevin Mulligan, David Sander, Julien Deonna
Chemistry, Biology, NeuroscienceChristoph Steinbeck, Nicolas le Novère, Colin Batchelor,
David Osumi-Sutherland, Jane Lomax, Jessica Turner, Angela Laird