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Phylogenetic trait mapping to find the function of a divergent fungal actin (iced)
Can phylogenetic trait mapping reveal the function of a structurally divergent actin isoform conserved across fungi, by finding a species-level trait that predicts its presence or absence?
How to read these graphs
A discourse graph breaks a piece of research into typed one-sentence nodes and draws how they bear on one another. The grammar is that of Discourse Graphs (Chan and Akamatsu). Read each graph left to right: a question, the experiments that addressed it, the results they produced, and the hypothesis every result is drawn against.
- QUE Question
- What the work set out to answer.
- HYP Hypothesis
- The answer the authors expected. Every result earns one edge against it.
- EXP Experiment
- One attempt at the question: a trial arm, an assay, a survey, an analysis.
- RES Result
- One finding from an experiment, with where in the source it comes from.
- ISS Issue
- An open question or untried branch the work leaves for someone else.
- addresses
- An experiment addresses the question.
- produces
- An experiment produces a result.
- supports
- A positive result that backs the hypothesis.
- opposes
- A negative result that counts as evidence against the hypothesis, or a refutation of an earlier claim.
- informs
- A partial or mixed result that bears on the hypothesis without settling it.
- consistent with
- A negative or inconclusive result that does not count either way: no positive control passed, or there is no sensitivity or power statement, so the absence of an effect cannot be told from a measurement that failed.
- relation
- A thin dotted line: a link the source itself states between two experiments, such as one being derived from another.
A dashed box marks a result the rule above counts as uninformative, or an issue. In the drawing, click a node to jump to its text below.
The graph
Read left to right. The question (QUE) is addressed by 3 experiments (EXP), each of which produces results (RES), and each result bears on the hypothesis (HYP) with one of four edges. 4 support it, 0 oppose it, 0 inform it, and 7 are merely consistent with it because the informativeness rule would not count them as evidence either way. Click a node to jump to its full text below.
- supports positive finding
- opposes informative negative, or refutation
- informs partial finding
- consistent with inconclusive or uninformative: no positive control passed, or no sensitivity statement
- thin grey a relation the record itself states between two attempts
- dashed box a result the informativeness rule marks uninformative, or an issue
The grammar is that of Discourse Graphs (Chan and Akamatsu): QUE, HYP, EXP, RES and ISS nodes with supports, opposes and informs edges. Every node and edge is derived from fields already in the Negative-Results Record; the edge a finding earns is decided by its outcomeClass and informativeness. Issues (ISS) hang below the graph as a strip: the open questions and untried branches the path leaves for someone else to pick up.
Nodes
Question and hypothesis
- QUE
- Can phylogenetic trait mapping reveal the function of a structurally divergent actin isoform conserved across fungi, by finding a species-level trait that predicts its presence or absence?
- HYP
- Test whether phylogenetic trait mapping can reveal the function of a structurally divergent actin isoform found across fungi, by asking whether any of six species-level fungal traits predicts the presence or absence of that isoform.
Experiments (3 attempts)
| Node | Attempt | Type | Headline | JSON | |
|---|---|---|---|---|---|
| EXP | ProteinCartography expands the divergent fungal actin set to 436 proteins across 412 strains 436 divergent actins spanning 412 strains, after combining LC04 and LC11 with the original LC14 more than 93% of the extended set is fungal; the next most represented kingdom, Metazoa, is 2% | computational | positive | record | |
| EXP | The divergent fungal actin is evolutionarily labile across the fungal kingdom the fraction of species possessing a DFA varies widely across fungal orders and is neither zero nor one for many orders, so DFA appears evolutionarily labile in contrast to canonical actin, which is highly conserved | computational | positive | record | |
| EXP | None of six curated fungal traits predicts the presence of a divergent fungal actin for all four discrete traits the independent-evolution model was more likely; neither continuous trait explained DFA presence or absence; no correlation was detected between DFA presence and any trait investigated | computational | inconclusive-no-positive-control | record |
Results (11 findings)
| Node | Finding | Id | Outcome and informativeness | Edge | JSON |
|---|---|---|---|---|---|
| RES | How many structurally similar divergent actins exist beyond the original cluster, and in how many strains? target: divergent fungal actin protein family; divergent actin proteins in the extended set = 436 (n = 412) | extended-setin arcadia-dfa-cluster-expansion | positivenot-applicable rule applies to negative and inconclusive findings only | supports HYP | record |
| RES | Is the extended set of divergent actins still overwhelmingly fungal? target: kingdom distribution of the divergent actin family; share of the extended set found in fungal species = more than 93% % | fungal-specificityin arcadia-dfa-cluster-expansion | positivenot-applicable rule applies to negative and inconclusive findings only | supports HYP | record |
| RES | Do fungal species that carry a divergent actin carry more than one? target: divergent actin copy number per species; share of divergent-actin-carrying species with exactly one copy = at least 95% % | single-copyin arcadia-dfa-cluster-expansion | positivenot-applicable rule applies to negative and inconclusive findings only | supports HYP | record |
| RES | Is the divergent fungal actin evolutionarily conserved across the fungal kingdom, or labile? target: divergent actin presence across fungal orders; fraction of species carrying a divergent actin, per fungal order = variable across and within orders, neither zero nor one for many orders (n = 853) | distribution-labilein arcadia-dfa-distribution | positivenot-applicable rule applies to negative and inconclusive findings only | supports HYP | record |
| RES | Does growth form predict the presence or absence of a divergent fungal actin across species? target: growth form; Akaike information criterion of the best independent-evolution model = 69.34 (n = 24) | trait-growth-formin arcadia-dfa-trait-association | inconclusive-no-positive-controluninformative no positive control; no negative control; no sensitivity or power statement | consistent-with HYP | record |
| RES | Does trophic mode predict the presence or absence of a divergent fungal actin across species? target: trophic mode; Akaike information criterion of the best independent-evolution model = 211.79 (n = 63) | trait-trophic-modein arcadia-dfa-trait-association | inconclusive-no-positive-controluninformative no positive control; no negative control; no sensitivity or power statement | consistent-with HYP | record |
| RES | Does ascus dehiscence predict the presence or absence of a divergent fungal actin across species? target: ascus dehiscence; Akaike information criterion of the best independent-evolution model = 30.06 (n = 13) | trait-ascus-dehiscencein arcadia-dfa-trait-association | inconclusive-no-positive-controluninformative no positive control; no negative control; no sensitivity or power statement | consistent-with HYP | record |
| RES | Does auxin-responsive promoter predict the presence or absence of a divergent fungal actin across species? target: auxin-responsive promoter; Akaike information criterion of the best independent-evolution model = 144.88 (n = 71) | trait-auxin-responsive-promoterin arcadia-dfa-trait-association | inconclusive-no-positive-controluninformative no positive control; no negative control; no sensitivity or power statement | consistent-with HYP | record |
| RES | Does spore length predict the presence or absence of a divergent fungal actin across species? target: spore length; slope of the trait on divergent actin presence, phylogeny-corrected logistic regression = 0.64 (n = 10) | trait-spore-lengthin arcadia-dfa-trait-association | inconclusive-no-positive-controluninformative no positive control; no negative control; no sensitivity or power statement | consistent-with HYP | record |
| RES | Does spore width predict the presence or absence of a divergent fungal actin across species? target: spore width; slope of the trait on divergent actin presence, phylogeny-corrected logistic regression = 0.71 (n = 10) | trait-spore-widthin arcadia-dfa-trait-association | inconclusive-no-positive-controluninformative no positive control; no negative control; no sensitivity or power statement | consistent-with HYP | record |
| RES | Does any of the six curated fungal traits predict the presence or absence of a divergent fungal actin? target: divergent fungal actin function, inferred from trait association; traits showing a correlated evolutionary trajectory with divergent actin presence = 0 (n = 6) | trait-overallin arcadia-dfa-trait-association | inconclusive-no-positive-controluninformative no positive control; no negative control; no sensitivity or power statement | consistent-with HYP | record |
Relations between attempts
arcadia-dfa-distributionwasDerivedFromarcadia-dfa-cluster-expansionarcadia-dfa-trait-associationwasDerivedFromarcadia-dfa-distributionlability motivated the search for an adaptive trait associationarcadia-dfa-trait-associationwasDerivedFromarcadia-dfa-cluster-expansion
Issues (5 open questions and untried branches)
- ISS What function do divergent fungal actins perform, given conserved ATP-binding residues but poorly conserved polymerization residues? (open-question)
- ISS Would a trait panel chosen for biological relevance rather than data availability recover an association? (open-question)
- ISS Expand the range of traits tested for correlation with DFA presence, which would require more complete datasets covering multiple species whose DFA status can be established; fungal ecology groups and mycologists may have the tools and knowledge to generate such information. (proposed-by-authors)
- ISS Focus on genetic traits using public genomic information: search for correlation between DFA presence or absence and the presence or absence of gene families across genomes of species with confident DFA status. (proposed-by-authors)
- ISS Probe DFA function directly by knocking out the DFA in a genetically tractable species and characterising the resulting phenotypes. (proposed-by-authors)