Transcript Phenomics for Neuropsychology

D Stott Parker1, WW Chu1, FW Sabb3, AW Toga2, RM Bilder3
1UCLA Computer Science Dept, 2Laboratory of Neuroimaging,
3Dept
of Psychiatry & Biobehavioral Sciences
Hypothesis Web Project
NIH RL1LM009833
PubAtlas is a
“PubMed
BLAST-query”
service for two
term sets/lexica
result:
contingency table
for all queries
(X AND Y) where
X,Y are terms in
the two lexica
www.pubatlas.org
PubAtlas Lexica:
• term: definition pairs
Term Name :
PubMed Query
• optional hierarchical structure
Lexicon as:
• concept base
• ontology
• user-defined term hierarchy
(personalized MeSH hierarchy)
• domain-specific query language
`Concept BLASTing’ seeks
useful associations, much
like microarray analysis
Lexicon1 = X hierarchy
Lexicon2 = Y hierarchy
PubAtlas
Literature Map:
MEDLINE / PubMed as a
bioscience association base
(X AND Y)
association table
semi-automated
generation of a
review paper -but thorough
and remaining
up-to-date
previous
PubMed
extensions
AliBaba:
Anne O'Tate:
BioIE:
ClusterMed:
ConceptLink:
GoPubMed:
HubMed:
PubFocus:
PubGene:
PubMatrix:
PubMed Assistant:
PubNet:
PubReMiner:
Relemed:
SLIM:
VisualNet:
XplorMed:
Desirable extension features
graph:
visual:
…)
friendly:
better interface:
exploration:
summarization:
map:
extraction:
relevance:
powerful:
"PubMed" [TIAB] AND ("graph" [TIAB] OR "network" [TIAB] OR "diagram" [TIAB])
"PubMed" [TIAB] AND ("visual" [TIAB] OR "visualizing" [TIAB] OR "visualization" [TIAB]
"PubMed"
"PubMed"
"PubMed"
"PubMed"
"PubMed"
"PubMed"
"PubMed"
"PubMed"
[TIAB]
[TIAB]
[TIAB]
[TIAB]
[TIAB]
[TIAB]
[TIAB]
[TIAB]
AND
AND
AND
AND
AND
AND
AND
AND
"AliBaba" [TIAB] AND "PubMed" [TIAB]
"Anne O'Tate" [TIAB]
"BioIE" [TIAB]
"ClusterMed" [TIAB]
"ConceptLink" [TIAB]
"GoPubMed" [TIAB]
"HubMed" [TIAB]
"PubFocus" [TIAB]
"PubGene" [TIAB]
"PubMatrix" [TIAB]
"PubMed Assistant" [TIAB]
"PubNet" [TIAB]
"PubReMiner" [TIAB]
"Relemed" [TIAB]
"Muin M" [au] AND "SLIM" [TIAB]
"VisualNet" [TIAB] OR "Visual Net" [TIAB]
"XplorMed" [TIAB]
("friendly" [TIAB] OR "flexible" [TIAB])
("interface" [TIAB] OR "interaction" [TIAB] OR "query" [TIAB]) …)
("exploration" [TIAB] OR "explore" [TIAB] OR "discovery" [TIAB] …)
(summariz* [TIAB] OR digest* [TIAB])
("mapping" [TIAB] OR "map" [TIAB] OR "mapped" [TIAB])
(extract* [TIAB] OR identif* [TIAB])
("relevance" [TIAB] OR "ranking" [TIAB] OR "ordering" [TIAB])
("powerful" [TIAB] OR "extended" [TIAB] OR "advanced" [TIAB])
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PubAtlas as a tool for concept “BLASTing”
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Moving towards shared, user-defined query/concept languages
Visual literature search with concept maps / literature maps
Building on familiar association mining metaphor
Extending PubMed with temporal indexing / concept evolution
Real uses: semi-automated reviews, knowledge mgmt, ...
Applications in Phenomics
 Phenotypes are often naturally represented as queries
 Promising applications in interdisciplinary collaboration
Who at UCLA works on
Dopamine Receptors?
Many possibilities for
interdisciplinary
collaboration
Lori Altshuler:
Stephen Marder:
Carrie Bearden:
Ty Cannon:
Michael Phelps:
John Mazziotta:
Paul Thompson:
Arthur Toga:
Roger Woods:
Bob Bilder:
Nelson Freimer:
.
.
.
Altshuler Lori
Marder Stephen
Bearden Carrie
Cannon Tyrone
Phelps Michael
Mazziotta John
Thompson Paul M
Toga Arthur
Woods Roger
Bilder Robert
Freimer Nelson
[FAU]
[FAU]
[FAU]
[FAU]
[FAU]
[FAU]
[FAU]
[FAU]
[FAU]
[FAU]
[FAU]
OR
OR
OR
OR
OR
OR
OR
OR
OR
OR
OR
Altshuler LL
Marder SR
Bearden CE
Cannon TD
Phelps ME
Mazziotta J
Thompson PM
Toga A
Woods RP
Bilder RM
Freimer N
Map of publications in
which people X, Y both
occur as authors
[AU]
[AU]
[AU]
[AU]
[AU]
[AU]
[AU]
[AU]
[AU]
[AU]
[AU]
Historical map of
interdisciplinary
collaboration at
UCLA over 10 yrs
2008
2006
2004
2002
2000
1998
Visualization and
interaction along
with standard mining
of association data
For term sets of
size M, N, PubAtlas
submits M+N
PubMed queries
This can scale to
hundreds or
thousands of terms
Diverse, complex
phenotypes can
be represented
as queries
(predicates)
-- denoting the
set of all relevant
documents
CNP_peo ple.terms
CNP.terms
Mem ory Mec hanisms.terms
ResponseInhi bition.terms
CNP_tea ms.terms
CNP_groups.terms
ADHD_gen es.terms
BP_gen es.terms
SZ_gen es.terms
CNP_gen es.terms
Pub Brain.t erms
UCLANeuroscienceFaculty.terms
MeSH_Amines.terms
MeSH_Aza_Compoun ds.terms
MeSH_Beh av ior.terms
MeSH_Brain_Anat om ical_Regio ns.terms
MeSH_Brain _Diseases.terms
MeSH_Catecholami nes.terms
MeSH_Cy toskeleton.terms
MeSH_dopa mine.terms
MeSH_Heterocy clic_Compoun ds_with_3 _rin gs.terms
MeSH_Heterocy clic_Compoun ds_with_4 _rin gs.terms
MeSH_Heterocy clic_Compoun ds_with_bridged _rin gs
MeSH_Hormones.terms
MeSH_Ment al_Disorders.terms
MeSH_Ment al_ Processes.terms
MeSH_Metab ol ic_Brain _Diseases.terms
MeSH_Neural_Pat hwa ys.terms
MeSH_Neurobeh av ioral_Ma nifestations.terms
MeSH_ne urobeh av ior.terms
MeSH_Neurodegen erativ e_Diseases.terms
MeSH_Neurons.terms
MeSH_Neurotoxicity_Disorders.terms
MeSH_Neurotransmitter_Age nts.terms
MeSH_Neurotransmitter_Receptors.terms
MeSH_Neurotransmitters.terms
MeSH_ne urotransmitter.terms
MeSH_Neurotransmitter_Transport_Proteins.terms
MeSH_Personal ity .t erms
MeSH_Primat es.terms
MeSH_Rode ntia.terms
MeSH_Sleep _Disorders.terms
MeSH_Su bstance_Related _Disorders.terms
CNP investigators, ordered alphabe tical ly
freque ntly-used terms in the CNP
freque ntly-used terms: CNP Mem ory Mec hanisms projec t
freque ntly-used terms: CNP Response Inhibition proje ct
CNP investigators, ordered by f iel d
CNP investigators, ordered by f iel d, with field names
a list of abou t 50 gen es possibly linked wit h ADHD
a list of abou t 25 gen es possibly linked wit h BP
a list of abou t 50 gen es possibly linked wit h SZ
a list of abou t 100 gen es possibly linked wit h ADHD/BP/SZ
Pub Brain vocabulary : 330 anatomica l regio ns of the brain
UCLA Neuroscienc e faculty, ordered alphabe tical ly
MeSH hierarc hy for Amines
MeSH hierarc hy for Aza Compounds
MeSH hierarc hy for Beh avior
MeSH hierarc hy for Brain Regio ns
MeSH hierarc hy for Brain Diseases
MeSH hierarc hy for Catecholami nes
MeSH hierarc hy for Cytoskeleto n
MeSH dop ami ne-relate d terms
MeSH hierarc hy for Heterocyclic Compounds (3 ring s)
MeSH hierarc hy for Heterocyclic Compounds (4 ring s)
MeSH hierarc hy for Heterocyclic Compounds (bridge d rin gs)
MeSH hierarc hy for Hormo nes
MeSH hierarc hy for Mental Disorders
MeSH hierarc hy for Mental Processes
MeSH hierarc hy for Metabol ic Pathways
MeSH hierarc hy for Ne ural Pathw ays
MeSH hierarc hy for Ne urobeh avioral Manifestatio ns
MeSH hierarc hy for neurobeh avior
MeSH hierarc hy for Ne urodegen erative Diseases
MeSH hierarc hy for Ne urons
MeSH hierarc hy for Ne urotoxicity Disorders
MeSH hierarc hy for Ne urotransmit ter Age nts
MeSH hierarc hy for Ne urotransmit ter Receptors
MeSH hierarc hy for Ne urotransmit ters
MeSH hierarc hy for neurotransmit ter
MeSH hierarc hy for Ne urotransmit ter Transort Proteins
MeSH hierarc hy for Personal ity
MeSH hierarc hy for Prima tes
MeSH hierarc hy for Ro dentia
MeSH hierarc hy for Slee p
MeSH hierarc hy for Substance-relate d Disorders
PubMed / MEDLINE =
central phenomics
database
paced auditory serial addition
"nback"

…
Wisconsin card sorting
N-back
Sternberg
choice reaction time
Stroop
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
("nback" OR “n-back” OR "wisconsin card
sorting" OR "sternberg" OR "working
memory capacity" OR "stroop" OR "choice
reaction time" OR "paced auditory serial
addition" OR "pasat" OR "digit span" OR
"delayed match to sample")
Queries (like “n-back test”) can be expanded with terms
related to their target concept (like working memory),
using statistical models to identify better expansions.
Expansion can improve precision and recall of queries
that are being used as models of concepts/phenotypes

PubAtlas as a tool for concept “BLASTing”







Lexica are concept bases / user-defined query languages
PubAtlas constructs concept maps / literature maps
Extends PubMed with temporal indexing
Multiple features for exploration, visualization
Real uses: semi-automated reviews, who is doing what, ...
Many interesting directions for further work
Applications in Phenomics
 Phenotypes are often naturally represented as queries
 Promising applications in interdisciplinary collaboration