hypothesis-generation
Formulate evidence-bounded scientific questions, candidate hypotheses, rival explanations, causal or associational claims, discriminating predictions, measurements, and preregistration-ready analysis plans. Use when turning observations or preliminary findings into transparent, testable research pla
By k-dense-ai · 1,567 installs
npx skills add k-dense-ai/scientific-agent-skills --skill hypothesis-generation
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Scientific Hypothesis Generation
Turn an observation into a transparent set of candidate explanations and tests. A hypothesis is a proposal to be challenged, not a finding, fact, diagnosis, or recommendation.
Non negotiable boundaries
Before using unpublished, sensitive, controlled, personal, proprietary, export controlled, or security relevant material:
1. Confirm authorization and the applicable institutional, funder, publisher, data use, privacy, and AI policies.
2. Keep the material local unless an authorized human explicitly approves a named external destination and data scope.
3. Minimize inputs. Do not place sensitive or unpublished data in web searches or external AI systems without authorization.
4. Stop at the appropriate human, animal, biosafety, dual use, data governance, or regulatory gate.
Never:
present a hypothesis, mechanism, causal effect, citation, or apparent pattern as established evidence;
claim novelty because a quick search found nothing;
infer causation from association, temporal order alone, predictive accuracy, or model output;
supply patient specific diagnosis, treatment, dose, prognosis, or other clinical advice;
provide harmful experimental optimization or operational detail for pathogens, toxins, weapons, evasion, or other misuse;
bypass IRB/REC, IACUC, IBC, biosafety, dual use, privacy, legal, or regulatory review;
fabricate sources, identifiers, search coverage, data, results, approvals, or preregistration;
automatically score, rank, select, accept, or reject scientific hypotheses.
If a request crosses a safety gate, produce only a high level risk/oversight note and route it to the qualified local authority. Do not continue with operational detail.
Keep the objects distinct
Object Meaning
Observation What was measured, noticed, or reported, with provenance and uncertainty
Research question The answerable question that defines scope
Hypothesis A candidate explanatory or relational proposition
Mechanism The proposed process connecting conditions to an outcome
Causal estimand The precisely defined causal contrast to estimate
Prediction An observable implication derived before checking the target result
Alternative explanation A rival account, including bias or non causal explanations
Null hypothesis A specified no effect/no difference model used by an analysis
Negative control A control expected not to operate through the proposed mechanism
Operationalization How a construct becomes a variable, measurement, intervention, or category
Analysis plan Prespecified transformations, models, contrasts, uncertainty, and decision rules
Evidence Observations or sources that bear on a claim; never the claim itself
Do not collapse these labels. A mechanistic story is not a prediction; a prediction is not evidence; rejection of one null does not prove a mechanism; support for one candidate does not eliminate unconsidered rivals.
Workflow
1. Run the scope and safety gate
Record:
accountable human owner and intended use;
data sensitivity, authorization, retention, and permitted processing;
affected people, animals, ecosystems, communities, or security interests;
required ethics, feasibility, biosafety, dual use, and regulatory reviews;
unresolved blocks and domain expertise needed.
No script approval is an ethics, safety, regulatory, or scientific approval.
2. Freeze the observation
Write the observation before interpretation:
measurement or source;
population, system, place, and time;
unit of observation and unit of analysis;
uncertainty, missingness, exclusions, and preprocessing;
whether the pattern was expected, exploratory, or selected after viewing results.
Use “reported,” “observed,” or “associated,” not causal language, unless a causal design and estimand justify it.
3. Frame the research question
Choose a framework only when it fits:
PICO/PICOT for intervention/effectiveness questions: population, intervention, comparator, outcome, and optionally time.
PECO for exposure questions.
Population–index test–reference standard–target condition for diagnostic accuracy.
Population–prognostic factor–outcome–time for prognosis.
A domain specific construct–context–outcome frame for qualitative, descriptive, mechanistic, or theoretical work.
PICO is not a universal template. Define stakeholders, context, boundaries, feasibility, and what answer would change knowledge or practice. FINER is a question refinement mnemonic—Feasible, Interesting, Novel, Ethical, Relevant—not a scoring system. Treat “Novel” as unresolved until a documented, fit for purpose search and expert review support it.
4. Establish a dated evidence boundary
Search before making literature dependent statements. Prefer primary research, official policies, primary methods papers, current reporting guidelines, and systematic reviews used for orientation.
Record:
search date and cutoff;
databases/indexes, queries, filters, and screening boundary;
included and excluded source types;
sources supporting, challenging, or contextualizing each claim;
known access, language, database, and time limitations.
A search can establish what was searched, not universal absence. Say “not located within the documented search boundary,” never “no prior work exists.” Use assets/search boundary template.json , assets/evidence ledger template.csv , and references/literature search strategies.md .
5. Generate rivals before choosing tests
Create multiple candidates from genuinely different explanatory classes when plausible:
proposed mechanism;
measurement or processing artifact;
confounding or common cause;
selection or attrition;
conditioning on a collider;
reverse causation;
temporal, contextual, or boundary condition differences;
stochastic variation;
competing mechanisms at another scale.
Generate an initial rival set independently before AI assisted expansion to reduce anchoring and homogenization. Do not force a fixed number or false symmetry. Keep every candidate labeled candidate .
Platt’s strong inference pattern motivates alternative hypotheses and crucial tests, but failed alternatives do not make the survivor true. Unknown alternatives, auxiliary assumptions, measurement error, and mixed mechanisms remain possible.
6. Declare the claim type and estimand
Classify each target as:
descriptive;
associational;
predictive;
causal;
mechanistic.
For a causal target, define before analysis:
target population or system;
intervention/exposure and comparator;
outcome and time horizon;
population level summary;
treatment versions and intercurrent event handling where relevant;
identification assumptions and target trial/design analogue.
Document confounding, selection, collider, measurement, and reverse causation risks separately. An observational causal estimate remains assumption dependent. Use references/causal inference and claims.md .
7. Derive discriminating predictions
For every candidate:
1. State conditions and boundary conditions.
2. Name the observable and measurement.
3. State the expected pattern and uncertainty.
4. State a result incompatible with the candidate under declared assumptions.
5. Contrast the expected result with at least one rival.
6. Define indeterminate outcomes and what would be learned from them.
Prefer tests where rivals predict meaningfully different outcomes. Add positive, procedural, and negative controls when scientifically appropriate. A negative control must be incapable of operating through the target mechanism while sharing relevant bias pathways; it is not a decorative untreated group.
Use assets/prediction rival matrix template.csv and assets/falsification controls template.json .
8. Operationalize and validate measurement
For every construct record:
variable role and operational definition;
population/system, unit, timing, and conditions;
instrument/method, calibration, quality control, and masking;
reliability/repeatability;
validity evidence and applicability;
missingness, detection limits, transformations, cut points, and their rationales;
measurement invariance or cross group comparability when relevant;
foreseeable measurement bias and limitations.
Do not treat a convenient proxy as the construct itself. Validate with:
9. Match design and analysis to the claim
Specify:
sampling, experimental unit, allocation, randomization, masking, and controls;
inclusion/exclusion and stopping rules;
sample size, precision, or information rationale based on declared assumptions;
outcomes, contrasts, estimands, models, effect measures, and uncertainty;
missing data and intercurrent event handling;
multiplicity across outcomes, models, subgroups, looks, and hypotheses;
assumptions, diagnostics, robustness, and sensitivity analyses;
replication or independent validation plan;
what is confirmatory versus exploratory.
Do not use universal sample size minima. Do not interpret a thresholded p value as the probability a hypothesis is true or as effect importance. See references/experimental design patterns.md .
For intervention trials, use the current SPIRIT 2025 protocol guidance and CONSORT 2025 reporting guidance where applicable. These improve completeness; they do not certify design quality, ethics, or regulatory compliance.
10. Prevent HARKing and expose deviations
Before accessing the target outcomes, timestamp the question, candidates, predictions, outcomes, exclusions, transformations, analysis, multiplicity, missing data plan, and stopping rule when feasible.
Afterward:
label data dependent ideas and analyses exploratory;
preserve and report planned analyses;
list deviations with date, rationale, who decided, and expected impact;
never rewrite an observed pattern as an a priori prediction.
Preregistration is a transparent plan, not a ban on adaptation. Registered Reports add results blind peer review and in principle acceptance under journal policy. See references/preregistration and open science.md .
11. Plan replication and updating
Distinguish:
reproducibility: consistent computational results from the same data/code/conditions;
replicability: consistency across studies collecting new data for the same question.
Preserve provenance, versions, code, materials, and decision logs when sharing is authorized. Plan independent replication or transport tests across relevant boundaries. Update candidate status when contrary, null, or replication evidence arrives; do not hide negative results.
12. Apply human accountability
The accountable human must verify:
every citation and source to claim link;
domain plausibility and measurement validity;
causal assumptions and statistical design;
ethics, feasibility, safety, privacy, and regulatory status;
all AI assisted text, ideas, and citations;
whether broader expertise or community input is required.
AI can confabulate citations, anchor reasoning, and homogenize candidate sets. Record permitted AI use and material influence. Keep independent human ideation and rival generation in the process.
Local tool index
All CLIs are bounded, dependency free, local, deterministic, and non scoring:
Task Asset Command
Hypothesis record schema assets/hypothesis record template.json python3 scripts/validate hypothesis schema.py record.json
Measurement checklist assets/operationalization template.json python3 scripts/check operationalization.py checklist.json
Prediction/rival matrix assets/prediction rival matrix template.csv python3 scripts/validate prediction matrix.py matrix.csv
Claim language lint Annotated Markdown python3 scripts/lint causal claims.py draft.md
Falsification/controls assets/falsification controls temp