ogms ontology for general medical science 1
TRANSCRIPT
OGMSOntology for General Medical
Science
http://code.google.com/p/ogms
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Basic Formal Ontology
continuant occurrent
independentcontinuant
dependentcontinuant
organism
2http://www.ifomis.org/bfo
:.
Users of BFO
PharmaOntology (W3C HCLS SIG)
MediCognos / Microsoft Healthvault
Cleveland Clinic Semantic Database in Cardiothoracic Surgery
Major Histocompatibility Complex (MHC) Ontology (NIAID)
Neuroscience Information Framework Standard (NIFSTD) and Constituent Ontologies
Interdisciplinary Prostate Ontology (IPO)
Nanoparticle Ontology (NPO): Ontology for Cancer Nanotechnology Research
Neural Electromagnetic Ontologies (NEMO)
ChemAxiom – Ontology for Chemistry
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:.
Users of BFOOntology for Risks Against Patient Safety (RAPS/REMINE)
Interdisciplinary Prostate Ontology (IPO)
Nanoparticle Ontology (NPO): Ontology for Cancer Nanotechnology Research
Neural Electromagnetic Ontologies (NEMO)
ChemAxiom – Ontology for Chemistry
Ontology for Risks Against Patient Safety (RAPS/REMINE) (EU FP7)
IDO Infectious Disease Ontology (NIAID)
National Cancer Institute Biomedical Grid Terminology (BiomedGT)
US Army Biometrics Ontology
US Army Command and Control Ontology
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Basic Formal Ontology
continuant occurrent
independentcontinuant
dependentcontinuant
organism
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Continuants
• continue to exist through time, preserving their identity while undergoing different sorts of changes
• independent continuants – objects, things, ...
• dependent continuants – qualities, attributes, shapes, potentialities ...
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Occurrents
• processes, events, happenings– your life– this process of accelerated cell
division
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Qualitiestemperatureblood pressuremass...
are continuantsthey exist through time while undergoing changes
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Qualitiestemperature / blood pressure /
mass ...are dimensions of variation within the structure of the entitya quality is something which can change while its bearer remains one and the same
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A Chart representing how John’s temperature
changes
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A Chart representing how John’s temperature
changes
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John’s temperature,the temperature he has throughout his entire life, cycles through different determinate temperatures from one time to the next
John’s temperature is a physiology variable which, in thus changing, exerts an influence on other physiology variables through time
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BFO: The Very Top
continuant
independentcontinuant
dependentcontinuant
quality
occurrent
temperature 13
clear division of types and instances
independentcontinuant
dependentcontinuant
quality
temperature types
instances
organism
John John’s
temperature 14
Blinding Flash of the Obvious
temperature types
instances
organism
John John’s
temperature .
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inheres_in
temperature types
instances
John’s temperature
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37ºC37.1º
C37.5º
C37.2º
C37.3º
C37.4º
C
instantiates at t1
instantiates at t2
instantiates at t3
instantiates at t4
instantiates at t5
instantiates at t6
human types
instances
John
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embryo
fetus adultneonat
einfant child
instantiates at t1
instantiates at t2
instantiates at t3
instantiates at t4
instantiates at t5
instantiates at t6
human phase types
instances
John
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embryo
stage
fetusstage
adultstage
neonate
stage
infantstage
childstage
has at t1 has at t2 has at t3 has at t4 has at t5 has at t6
Canonical whole (human) organism stages
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blastula stage
gastrula stage
coronary heart disease
John’s coronary heart disease
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asymptomatic (‘silent’) infarction
early lesions and small
fibrous plaques
stable angina
surface disruption of plaque
unstable angina
instantiates at t1
instantiates at t2
instantiates at t3
instantiates at t4
instantiates at t5
time
hand
John’s hand
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fistunclenche
d hand unclenche
d hand
instantiates at t1
instantiates at t2
instantiates at t3
time
folding hand, folding protein
Temperature subtypesDevelopment-stage
subtypes
are threshold divisions (hence we do not have sharp boundaries, and we have a certain degree of choice, e.g. in how many subtypes to distinguish, though not in their ordering)
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independentcontinuant
dependentcontinuant
quality
temperature types
instances
organism
John John’s
temperature
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independentcontinuant
dependentcontinuant
quality
temperature
organism
John John’s
temperature
occurrent
process
course of temperature
changes
John’s temperature history
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independentcontinuant
dependentcontinuant
quality
temperature
organism
John John’s
temperature
occurrent
process
life of an organism
John’s life
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BFO: The Very Top
continuant occurrent
independentcontinuant
dependentcontinuant
quality disposition
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Disposition- of a glass vase, to shatter if dropped- of a human, to eat - of a banana, to ripen- of John, to lose hair
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Dispositionif it ceases to exist, then its bearer is physically changedits realization occurs when its bearer is in some special physical circumstancesits realization is what it is in virtue of the bearer’s physical make-up
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:.
Function - of liver: to store glycogen- of birth canal: to enable transport- of eye: to see- of mitochondrion: to produce ATP
functions are dispositions which are designed or selected for
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independentcontinuant
dependentcontinuant
function
to seeeye
John’s eye function of John’s eye: to see
occurrent
process
process of seeing
John seeing
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Physical Disorder
:.
Physical Disorder
– independent continuant (part of the extended organism)
A causally linked combination of physical components that is clinically abnormal.
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Clinically abnormal
– (1) not part of the life plan for an organism of the relevant type (unlike aging or pregnancy),
– (2) causally linked to an elevated risk either of pain or other feelings of illness, or of death or dysfunction, and
– (3) such that the elevated risk exceeds a certain threshold level.*
*Compare: baldness33
Big Picture
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Pathological Process=def. A bodily process that is a manifestation of a disorder and is clinically abnormal.
Disease =def. – A disposition to undergo pathological processes that exists in an organism because of one or more disorders in that organism.
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Cirrhosis - environmental exposure
• Etiological process - phenobarbitol-induced hepatic cell death– produces
• Disorder - necrotic liver– bears
• Disposition (disease) - cirrhosis– realized_in
• Pathological process - abnormal tissue repair with cell proliferation and fibrosis that exceed a certain threshold; hypoxia-induced cell death– produces
• Abnormal bodily features– recognized_as
• Symptoms - fatigue, anorexia• Signs - jaundice, enlarged spleen
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Influenza - infectious
• Etiological process - infection of airway epithelial cells with influenza virus
– produces
• Disorder - viable cells with influenza virus
– bears
• Disposition (disease) - flu
– realized_in
• Pathological process - acute inflammation
– produces
• Abnormal bodily features
– recognized_as
• Symptoms - weakness, dizziness
• Signs - fever 37
Dispositions and Predispositions
All diseases are dispositions; not all dispositions are diseases.
Predisposition to Disease
=def. – A disposition in an organism that constitutes an increased risk of the organism’s subsequently developing some disease.
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Huntington’s Disease – genetic (sure-fire)
• Etiological process - inheritance of >39 CAG repeats in the HTT gene– produces
• Disorder - chromosome 4 with abnormal mHTT– bears
• Disposition (disease) - Huntington’s disease– realized_in
• Pathological process - accumulation of mHTT protein fragments, abnormal transcription regulation, neuronal cell death in striatum– produces
• Abnormal bodily features– recognized_as
• Symptoms - anxiety, depression• Signs - difficulties in speaking and swallowing
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HNPCC - genetic pre-disposition• Etiological process - inheritance of a mutant mismatch repair gene
– produces• Disorder - chromosome 3 with abnormal hMLH1
– bears• Disposition (disease) - Lynch syndrome
– realized_in• Pathological process - abnormal repair of DNA mismatches
– produces• Disorder - mutations in proto-oncogenes and tumor suppressor
genes with microsatellite repeats (e.g. TGF-beta R2)– bears
• Disposition (disease) - non-polyposis colon cancer– realized in
• Symptoms (including pain)
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http://code.google.com/p/ogms
Disease =def. – A disposition to undergo pathological processes that exists in an organism because of one or more disorders in that organism.
Disease course =def. – The aggregate of processes in which a disease disposition is realized.
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independentcontinuant
dependentcontinuant
disposition
diseasedisorder
John’s disordered
heart
John’s coronary heart
disease
occurrent
process
course of disease
course of John’s disease
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OGMS Applied• OGMS is the Ontology for General Medical Science,
which provides definitions for all the terms (such as ‘disorder’, ‘symptom’, and so forth) See: http://code.google.com/p/ogms/
Axes where PRO can make contributions are, I think, as follows:• Etiological Process
• Disorder
• Pathological Process
• Laboratory Test Result
• (Drug) Treatment
Examples of the first 4 are given in slides 3ff.
Big Picture
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Influenza - infectious
• Etiological process - infection of airway epithelial cells with influenza virus
– produces
• Disorder - viable cells with influenza virus
– bears
• Disposition (disease) - flu
– realized_in
• Pathological process - acute inflammation
– produces
• Abnormal bodily features
– recognized_as
• Symptoms - weakness, dizziness
• Signs - fever
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - rule out influenza suggests
Laboratory tests produces
Test results - elevated serum antibody titers used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease flu
But the disorder also induces normal physiological processes (immune response) that can results in the elimination of the disorder (transient disease course).
Huntington’s Disease - genetic
• Etiological process - inheritance of >39 CAG repeats in the HTT gene– produces
• Disorder - chromosome 4 with abnormal mHTT– bears
• Disposition (disease) - Huntington’s disease– realized_in
• Pathological process - accumulation of mHTT protein fragments, abnormal transcription regulation, neuronal cell death in striatum– produces
• Abnormal bodily features– recognized_as
• Symptoms - anxiety, depression• Signs - difficulties in speaking and
swallowing
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - rule out Huntington’s suggests
Laboratory tests produces
Test results - molecular detection of the HTT gene with >39CAG repeats used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease Huntington’s disease
HNPCC - genetic pre-disposition
• Etiological process - inheritance of a mutant mismatch repair gene– produces
• Disorder - chromosome 3 with abnormal hMLH1– bears
• Disposition (disease) - Lynch syndrome– realized_in
• Pathological process - abnormal repair of DNA mismatches– produces
• Disorder - mutations in proto-oncogenes and tumor suppressor genes with microsatellite repeats (e.g. TGF-beta R2)– bears
• Disposition (disease) - non-polyposis colon cancer
Cirrhosis - environmental exposure
• Etiological process - phenobarbitol-induced hepatic cell death
– produces
• Disorder - necrotic liver
– bears
• Disposition (disease) - cirrhosis
– realized_in
• Pathological process - abnormal tissue repair with cell proliferation and fibrosis that exceed a certain threshold; hypoxia-induced cell death
– produces
• Abnormal bodily features
– recognized_as
• Symptoms - fatigue, anorexia
• Signs - jaundice, splenomegaly
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - rule out cirrhosis suggests
Laboratory tests produces
Test results - elevated liver enzymes in serum used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease cirrhosis
Systemic arterial hypertension
• Etiological process – abnormal reabsorption of NaCl by the kidney
– produces
• Disorder – abnormally large scattered molecular aggregate of salt in the blood
– bears
• Disposition (disease) - hypertension
– realized_in
• Pathological process – exertion of abnormal pressure against arterial wall
– produces
• Abnormal bodily features
– recognized_as
• Symptoms -
• Signs – elevated blood pressure
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - rule out hypertension suggests
Laboratory tests produces
Test results - used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease hypertension
Type 2 Diabetes Mellitus
• Etiological process –
– produces
• Disorder – abnormal pancreatic beta cells or abnormal muscle/fat cells
– bears
• Disposition (disease) – diabetes mellitus
– realized_in
• Pathological processes – diminished insulin production, diminished muscle/fat uptake of glucose
– produces
• Abnormal bodily features
– recognized_as
• Symptoms – polydipsia, polyuria, polyphagia, blurred vision
• Signs – elevated blood glucose and hemoglobin A1c
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - rule out diabetes mellitus suggests
Laboratory tests – fasting serum blood glucose, oral glucose challenge test, and/or blood hemoglobin A1c produces
Test results - used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease type 2 diabetes mellitus
Type 1 hypersensitivity to penicillin
• Etiological process – sensitizing of mast cells and basophils during exposure to penicillin-class substance
– produces
• Disorder – mast cells and basophils with epitope-specific IgE bound to Fc epsilon receptor I
– bears
• Disposition (disease) – type I hypersensitivity
– realized_in
• Pathological process – type I hypersensitivity reaction
– produces
• Abnormal bodily features
– recognized_as
• Symptoms – pruritis, shortness of breath
• Signs – rash, urticaria, anaphylaxis
Symptoms & Signs used_in
Interpretive process produces
Hypothesis - suggests
Laboratory tests – produces
Test results – occasionally, skin testing used_in
Interpretive process produces
Result - diagnosis that patient X has a disorder that bears the disease type 1 hypersensitivity to penicillin
Early Onset Alzheimer’s Disease
Disorder – mutations in APP, PSEN1 and PSEN2bears
Disposition – impaired APP processingrealized in
Pathological process – accumulation of intra- and extracellular protein in the brainproduces
Disorder – amyloid plaque and neurofibrillary tanglesbearsDisposition – of neurons to dierealized in Pathological process – neuronal loss
producesDisorder – cognitive brain regions damaged and reduced in size
bearsDisposition (disease) – Alzheimer’s dementia
realized inSymptoms – episodic memory loss and other cognitive domain impairment
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Arterial Aneurysm• Disposition – atherosclerosis
– realized in• Pathological process – fatty material collects within the walls of arteries
– produces• Disorder – artery with weakened wall
– bears• Disposition – of artery to become distended
– realized_in• Pathological process – process of distending
– produces• Disorder – arterial aneurysm
– bears• Disposition – of artery to rupture
– realized in• Pathological process – (catastrophic event) of rupturing
– produces• Disorder – ruptured artery, arterial system with dangerously low blood pressure
– bears• Disposition – circulatory failure
– realized in• Pathological process – exsanguination, failure of homeostasis
– produces• Death
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Hemorrhagic stroke
• Disorder – cerebral arterial aneurysm– bears
• Disposition – of weakened artery to rupture– realized in
• Pathological process – rupturing of weakened blood vessel– produces
• Disorder – Intraparenchymal cerebral hemorrhage– bears
• Disposition (disease) – to increased intra-cranial pressure– realized in
• Pathological process – increasing intra-cranial pressure, compression of brain structures– produces
• Disorder – Cerebral ischemia, Cerebral neuronal death– bears
• Disposition (disease) – stroke– realized in
• Symptoms – weakness/paralysis, loss of sensation, etc
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Ontology of Aging and Death
Ontology axioms (dying)
• dying part_of life of organism
• life of organism occupies temporal interval
• dying has_participant organism
• dying occupies temporal interval
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Ontology axioms – universal truths1. dying occupies temporal interval 2. every dying instance_of process3. every process occupies some temporal interval
1.is an assertion about types or universals*2.is an assertion about a relation between types and instances3. is an assertion about instances
*what ontology graphs represent59
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We know when dying ends
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Death
Process boundaries
Instants of Time
occupy
Dying
When does dying begin?
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Death
Process boundaries
Instants of Time
occupy
Dying
When does balding begin?
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An ontological question: what is aging?
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The Aging Process
Death
Processes in the Organism
Regions of Time
occupy
The Dying Process
Life of Organism
Orthomereology
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The Aging Process
Death
Processes in the Organism
Regions of Time
occupy
The Dying Process
(Normal) life of (normal) multicellular
organism
Aging part_of life of organism
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– Every instance of aging part_of life of some organism
NOT: aging has_part dying – given progeria
NOT: Life of organism has_part aging(a)a life may be cut short by early death(b)rejuvenation
http://www.sens.org/ 68
We focus in what follows on ‘normal aging’?
= non-premature aging which is not cut short by early death
There are certain processes which are normally part of the aging
process69
Carlos Lopez-Otin, et al., “The Hallmarks of Aging”, Cell 153, 2013
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Of the roughly 150,000 people who die each day across the globe, about two thirds die of age-related causes (senescence)
Hypothesis: age-related causes =def. processes of a sort which (i) are part of the normal aging process and (ii) occur at the stage in life that is normal for aging
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What does ‘normal’ mean?For anatomy we have an answer to this question
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Foundational Model of Anatomy
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Canonically (normally) human beings have 32 teeth• This is part of the Bauplan of human beings • US adults have an average of 24.92 teeth• Thus ‘normal’ ‘statistically normal’
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represents canonical adult human anatomy= the Bauplan generated by the coordinated expression of the human organism’s own structural genes*
*thus there is still a statistical dimension here, but not at the level of patient phenotypes (teeth lost in bar fights)
Foundational Model of Anatomy Ontology
Foundational Model of Anatomy (FMA)
Pleural Cavity
Pleural Cavity
Interlobar recess
Interlobar recess
Mesothelium of Pleura
Mesothelium of Pleura
Pleura(Wall of Sac)
Pleura(Wall of Sac)
VisceralPleura
VisceralPleura
Pleural SacPleural Sac
Parietal Pleura
Parietal Pleura
Anatomical SpaceAnatomical Space
OrganCavityOrganCavity
Serous SacCavity
Serous SacCavity
AnatomicalStructure
AnatomicalStructure
OrganOrgan
Serous SacSerous Sac
MediastinalPleura
MediastinalPleura
TissueTissue
Organ PartOrgan Part
Organ Subdivision
Organ Subdivision
Organ Component
Organ Component
Organ CavitySubdivision
Organ CavitySubdivision
Serous SacCavity
Subdivision
Serous SacCavity
Subdivision
part
_of
is_a
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Canonically (normally) human beings have 2 lungs• This is part of the Bauplan of human beings
Canonically (normally) death is the terminal boundary of a process of aging
• This is part of the life plan of human beings
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What makes premature aging non-normal?Answer: that it does not fit in the right way into the life plan for an organism of the relevant typeIt does not fit into the canonical cycle of stages generated by the coordinated expression of the organism’s own developmental genes
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Life plan (human, first 9 days)
From anatomy to development• Canonical Bauplan = no amputation
stumps, no effects of steroids, no webbed fingers …
• Canonical life plan = canonical sequence of life processes for an organism of this species (no early death through injury or famine, no life-changing childhood disease, no excessive studying of philosophy …) -
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Where do we find a good ontology of stages?
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In the life cycle of plants we have alternating generations
gametophyte = whole plant in haploid stage; male and female gametes fuse to produce the zygote from which the sporophyte arises
sporophyte = whole plant in diploid stage (the dominant form in vascular plants such as ferns); produces spores from which the gametophyte arises.
whole plant development stage
PO:0007033
gametophyte development stage
PO:0028003
sporophyte development stage
PO:0028002
life of whole plantPO:0025337
PP
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Life cycle of Selaginella apoda (Felsen Moosfarn)
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whole plant development
stagePO:0007033
gametophyte development
stagePO:0028003
sporophyte development
stagePO:0028002
life of whole plant
PO:0025337
plant spore stage
PO:0025375
gametophyte vegetative stage
PO:0025340
gametophyte dormant stagePO:0025342
gametophyte reproductive
stagePO:0025341
gametophyte senescent stage
PO:0025343
sporophyte senescent
stagePO:0007017
sporophyte dormant stagePO:0007132
sporophyte reproductive
stagePO:0007130
sporophyte vegetative stage
PO:0007134
plant zygote stage
PO:0028002
PP
is_apart_
of
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Plant Life Cycle (principal whole plant development stages)
84http://blog.botanybill.info/?p=1225
sporophyte senescent stagePO:0007017
Senescence for whole plants does not imply senescence
for plant parts
often fruit development on a whole plant is happening simultaneously with senescence of the plant
in some cases, fruit doesn’t ripen until after the vegetative parts of the plant are dead
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http://bioportal.bioontology.org
Canonical whole (human) organism stages
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blastula stage
gastrula stage
From birth to death
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whole human development stage
post-natal development stage
life of whole human
aging stage
reproductive stage
maturation stage
growth stage
P
How to understand the aging stage
• Aging not part of the life plan for multicellular organisms like us
• aging is a disease; it is a deviation (or set of deviations) from this life plan, which can in principle be rectified by treatment or engineering (SENS) – thus it is not a stage at all
• aging is a post-reproductive pseudo-stage: (some) organisms manage to survive after the (last genuine) stage where they can reproduce; to be alive in this pseudo-stage is a lucky accidentc
• Aging is part of the life plan; it is a genuine stage in the life of the organism, a reflection of its evolutionary program, and thus it must be in some sense adaptive
• what is programmed for by the genome cannot be a disease• characteristic disease-like correlates of aging are not diseases
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How to deal with the Boorsean problems raised by ‘typical diseases of old age’ (benign prostatic hypertrophy)?• old Boorse: they are not diseases because they are
statistically typical for the age group formed by aged people (they are like menopause …)
• new Boorse: they are diseases, because typicality is to be determined by the reference class formed by healthy young adults this seems ad hoc
See C. Boorse, “Replies to recent critics”, August 2012
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Boorse (Replies to critics) – it is not ad hoc: “biologists, though they catalogue immature stages, do not usually catalogue stages of senescence”
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old Boorse
• A disease [later, pathological condition] is a type of internal state which impairs health, i.e., reduces one or more functional abilities below typical efficiency in a way that is detrimental to their individual survival [or] reproduction
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new (pseudo-)Boorse
• A disease [later, pathological condition] in the aged is a type of internal state which impairs health, i.e., reduces one or more functional abilities below typical efficiency for young adults in a way that is detrimental to their individual survival [or] reproduction
• “All functional declines with age to far below the young-adult mean would be pathological. “
• So menopause is a disease
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