spatialquery.js 0.0.0-stage → 0.1.1

package/dist/fpgrowth.d.ts

@@ -0,0 +1,10 @@
+export type FrequentPattern = {
+    itemsets: string[];
+    support: number;
+    neighborIds?: string[];
+};
+export declare function findMaximalPatterns<T extends {
+    itemsets: string[];
+}>(patterns: T[]): T[];
+export declare function mineFrequentPatterns(transactions: string[][], minSupport: number, ifMax: boolean): Promise<FrequentPattern[]>;
+//# sourceMappingURL=fpgrowth.d.ts.map

package/dist/fpgrowth.d.ts.map

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package/dist/fpgrowth.js

@@ -0,0 +1,35 @@
+import { FPGrowth } from 'node-fpgrowth';
+// Keep only the maximal patterns: those that are not a proper subset of another pattern.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_utils.py#L68
+export function findMaximalPatterns(patterns) {
+    const sets = patterns.map(p => new Set(p.itemsets));
+    return patterns.filter((p, i) => !sets.some((other, j) => (j !== i
+        && other.size > sets[i].size
+        && p.itemsets.every(item => other.has(item)))));
+}
+// Mine frequent patterns from transactions of cell type labels.
+// Equivalent to the MultiLabelBinarizer + mlxtend fpgrowth + find_maximal_patterns
+// steps of build_fptree_dist / build_fptree_knn.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_utils.py#L454
+export async function mineFrequentPatterns(transactions, minSupport, ifMax) {
+    if (transactions.length === 0) {
+        return [];
+    }
+    // Transactions are binarized in Python, so duplicate cell types are collapsed.
+    const uniqueTransactions = transactions.map(t => Array.from(new Set(t)));
+    const fpgrowth = new FPGrowth(minSupport);
+    const itemsets = await fpgrowth.exec(uniqueTransactions);
+    // node-fpgrowth reports support as a count; mlxtend reports a fraction.
+    const byKey = new Map();
+    for (const { items, support } of itemsets) {
+        const sorted = items.toSorted();
+        byKey.set(JSON.stringify(sorted), { itemsets: sorted, support: support / transactions.length });
+    }
+    let patterns = Array.from(byKey.values());
+    if (ifMax) {
+        patterns = findMaximalPatterns(patterns);
+    }
+    // Sort by descending support, breaking ties by itemsets for a deterministic order.
+    return patterns.toSorted((a, b) => (b.support - a.support || JSON.stringify(a.itemsets).localeCompare(JSON.stringify(b.itemsets))));
+}
+//# sourceMappingURL=fpgrowth.js.map

package/dist/fpgrowth.js.map

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package/dist/index.d.ts

@@ -0,0 +1,6 @@
+export { generateObsIdToObsSetName, normalizeSpatialCoords, buildContext, buildGridPoints, findPatternsGrid, findPatternsRand, findFpKnn, findFpDist, computeMotifEnrichment, motifEnrichmentKnn, motifEnrichmentDist, motifCompositionKnn, motifCompositionDist, type InitParams, type SqContext, type MotifsParam, type EnrichmentMode, type MotifEnrichmentResult, type MotifCompositionRow, } from './single-fov.js';
+export { buildMultiContext, multiFindFpKnn, multiFindFpDist, findFpKnnFov, findFpDistFov, multiMotifEnrichmentKnn, multiMotifEnrichmentDist, multiMotifCompositionKnn, multiMotifCompositionDist, differentialAnalysisKnn, differentialAnalysisDist, differentialTestsKnn, differentialTestsDist, type FovInitParams, type SqMultiContext, type MultiFovMotifEnrichmentResult, type MultiFovMotifCompositionRow, type DifferentialResult, type DifferentialTestResult, } from './multi-fov.js';
+export { findMaximalPatterns, type FrequentPattern } from './fpgrowth.js';
+export { nestedMotifDescent } from './nested.js';
+export { applyFdrCorrection } from './stats.js';
+//# sourceMappingURL=index.d.ts.map

package/dist/index.d.ts.map

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package/dist/index.js

@@ -0,0 +1,6 @@
+export { generateObsIdToObsSetName, normalizeSpatialCoords, buildContext, buildGridPoints, findPatternsGrid, findPatternsRand, findFpKnn, findFpDist, computeMotifEnrichment, motifEnrichmentKnn, motifEnrichmentDist, motifCompositionKnn, motifCompositionDist, } from './single-fov.js';
+export { buildMultiContext, multiFindFpKnn, multiFindFpDist, findFpKnnFov, findFpDistFov, multiMotifEnrichmentKnn, multiMotifEnrichmentDist, multiMotifCompositionKnn, multiMotifCompositionDist, differentialAnalysisKnn, differentialAnalysisDist, differentialTestsKnn, differentialTestsDist, } from './multi-fov.js';
+export { findMaximalPatterns } from './fpgrowth.js';
+export { nestedMotifDescent } from './nested.js';
+export { applyFdrCorrection } from './stats.js';
+//# sourceMappingURL=index.js.map

package/dist/index.js.map

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package/dist/multi-fov.d.ts

@@ -0,0 +1,115 @@
+import { type InitParams, type SqContext, type MotifsParam, type MotifEnrichmentResult, type MotifCompositionRow, type EnrichmentMode } from './single-fov.js';
+import { type FrequentPattern } from './fpgrowth.js';
+export type FovInitParams = InitParams & {
+    datasetId: string;
+    datasetClass: string;
+};
+export type SqMultiContext = {
+    datasetIds: string[];
+    datasetClasses: string[];
+    contexts: SqContext[];
+};
+export declare function buildMultiContext(fovs: FovInitParams[]): SqMultiContext;
+type DatasetClassParam = {
+    datasetClass?: string | string[];
+};
+type MultiFindFpKnnParams = DatasetClassParam & {
+    ct: string;
+    k?: number;
+    minSupport?: number;
+    maxDist?: number;
+    ifMax?: boolean;
+};
+export declare function multiFindFpKnn(multi: SqMultiContext, params: MultiFindFpKnnParams): Promise<FrequentPattern[]>;
+type MultiFindFpDistParams = DatasetClassParam & {
+    ct: string;
+    maxDist?: number;
+    minSize?: number;
+    minSupport?: number;
+    ifMax?: boolean;
+};
+export declare function multiFindFpDist(multi: SqMultiContext, params: MultiFindFpDistParams): Promise<FrequentPattern[]>;
+type FindFpFovParams = {
+    ct: string;
+    datasetId: string;
+};
+export declare function findFpKnnFov(multi: SqMultiContext, params: FindFpFovParams & {
+    k?: number;
+    minSupport?: number;
+    maxDist?: number;
+}): Promise<FrequentPattern[]>;
+export declare function findFpDistFov(multi: SqMultiContext, params: FindFpFovParams & {
+    maxDist?: number;
+    minSize?: number;
+    minSupport?: number;
+}): Promise<FrequentPattern[]>;
+export type MultiFovMotifEnrichmentResult = Omit<MotifEnrichmentResult, 'neighborIds' | 'centerIds'> & {
+    neighborIds?: Record<string, string[]>;
+    centerIds?: Record<string, string[]>;
+};
+type MultiMotifEnrichmentKnnParams = DatasetClassParam & {
+    ct: string;
+    motifs?: MotifsParam;
+    k?: number;
+    minSupport?: number;
+    maxDist?: number;
+    returnCellIds?: boolean;
+    mode?: EnrichmentMode;
+};
+export declare function multiMotifEnrichmentKnn(multi: SqMultiContext, params: MultiMotifEnrichmentKnnParams): Promise<MultiFovMotifEnrichmentResult[]>;
+type MultiMotifEnrichmentDistParams = DatasetClassParam & {
+    ct: string;
+    motifs?: MotifsParam;
+    maxDist?: number;
+    minSize?: number;
+    minSupport?: number;
+    returnCellIds?: boolean;
+    mode?: EnrichmentMode;
+};
+export declare function multiMotifEnrichmentDist(multi: SqMultiContext, params: MultiMotifEnrichmentDistParams): Promise<MultiFovMotifEnrichmentResult[]>;
+export type MultiFovMotifCompositionRow = MotifCompositionRow & {
+    datasetId: string;
+};
+export declare function multiMotifCompositionKnn(multi: SqMultiContext, params: DatasetClassParam & {
+    ct: string;
+    motifs: MotifsParam;
+    k?: number;
+    maxDist?: number;
+}): MultiFovMotifCompositionRow[];
+export declare function multiMotifCompositionDist(multi: SqMultiContext, params: DatasetClassParam & {
+    ct: string;
+    motifs: MotifsParam;
+    maxDist?: number;
+}): MultiFovMotifCompositionRow[];
+export type DifferentialTestResult = {
+    itemsets: string[];
+    supports: Record<string, number[]>;
+    supportMean: Record<string, number>;
+    pValue: number;
+    adjPValue: number;
+    ifSignificant: boolean;
+    datasetClassHigherFrequency: string;
+};
+export type DifferentialResult = Pick<DifferentialTestResult, 'itemsets' | 'supportMean' | 'adjPValue'>;
+type DifferentialAnalysisKnnParams = {
+    ct: string;
+    datasetClasses: string[];
+    motifs?: MotifsParam;
+    k?: number;
+    minSupport?: number;
+    maxDist?: number;
+};
+export declare function differentialTestsKnn(multi: SqMultiContext, params: DifferentialAnalysisKnnParams): Promise<DifferentialTestResult[]>;
+export declare function differentialAnalysisKnn(multi: SqMultiContext, params: DifferentialAnalysisKnnParams): Promise<Record<string, DifferentialResult[]>>;
+type DifferentialAnalysisDistParams = {
+    ct: string;
+    datasetClasses: string[];
+    motifs?: MotifsParam;
+    maxDist?: number;
+    minSupport?: number;
+    minSize?: number;
+};
+export declare function differentialTestsDist(multi: SqMultiContext, params: DifferentialAnalysisDistParams): Promise<DifferentialTestResult[]>;
+export declare function differentialAnalysisDist(multi: SqMultiContext, params: DifferentialAnalysisDistParams): Promise<Record<string, DifferentialResult[]>>;
+export {};
+//# sourceMappingURL=multi-fov.d.ts.map

package/dist/multi-fov.d.ts.map

@@ -0,0 +1 @@
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package/dist/multi-fov.js

@@ -0,0 +1,325 @@
+// Port of the multi-FOV class spatial_query_multi.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py
+import { buildContext, findCellIndicesOfType, knnTransactions, radiusTransactions, centerQueryPoints, knnNeighborhood, radiusNeighborhood, countMotifs, computeMotifEnrichment, normalizeMotifs, normalizeMotifList, motifCompositionRows, assertEnrichmentMode, findFpKnn as findFpKnnSingle, findFpDist as findFpDistSingle, } from './single-fov.js';
+import { mineFrequentPatterns } from './fpgrowth.js';
+import { nestedMotifDescent } from './nested.js';
+import { applyFdrCorrection, fdrCorrection, mannWhitneyU, rankAverage, median, mean } from './stats.js';
+// Build the multi-FOV context object.
+// Unlike Python, which derives unique FOV names from the (possibly repeated) dataset names
+// ('name' -> 'name_0', 'name_1', ...), each FOV has an explicit ID and class.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py#L43
+export function buildMultiContext(fovs) {
+    const datasetIds = fovs.map(fov => fov.datasetId);
+    const duplicates = datasetIds.filter((id, i) => datasetIds.indexOf(id) !== i);
+    if (duplicates.length > 0) {
+        throw new Error(`Dataset IDs must be unique. Found duplicates: ${Array.from(new Set(duplicates)).join(', ')}`);
+    }
+    return {
+        datasetIds,
+        datasetClasses: fovs.map(fov => fov.datasetClass),
+        contexts: fovs.map(fov => buildContext(fov)),
+    };
+}
+// The datasets (FOVs) belonging to the selected classes (all classes if not provided).
+function selectFovs(multi, datasetClass) {
+    const validClasses = new Set(multi.datasetClasses);
+    const selected = datasetClass === undefined
+        ? validClasses
+        : new Set(typeof datasetClass === 'string' ? [datasetClass] : datasetClass);
+    for (const c of selected) {
+        if (!validClasses.has(c)) {
+            throw new Error(`Invalid dataset class: ${c}. Valid dataset classes are: ${Array.from(validClasses).join(', ')}`);
+        }
+    }
+    return multi.contexts
+        .map((context, i) => ({ datasetId: multi.datasetIds[i], datasetClass: multi.datasetClasses[i], context }))
+        .filter(fov => selected.has(fov.datasetClass));
+}
+// Throws if the cell type is absent from every FOV (selected or not, as in Python).
+function assertCellTypeInAnyFov(multi, ct) {
+    if (!multi.contexts.some(context => context.labels.includes(ct))) {
+        throw new Error(`Found no ${ct} in any datasets!`);
+    }
+}
+// Unique cell type labels across all FOVs.
+function allLabels(multi) {
+    return new Set(multi.contexts.flatMap(context => context.labels));
+}
+// Find frequent patterns within the k-NN neighborhoods of a cell type, pooling the
+// neighborhoods of all selected FOVs.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py#L116
+export async function multiFindFpKnn(multi, params) {
+    const { ct, datasetClass, k = 30, minSupport = 0.5, maxDist = 20, ifMax = true } = params;
+    assertCellTypeInAnyFov(multi, ct);
+    const transactions = selectFovs(multi, datasetClass).flatMap(({ context }) => (knnTransactions(context, findCellIndicesOfType(context, ct), k, maxDist)));
+    return mineFrequentPatterns(transactions, minSupport, ifMax);
+}
+// Find frequent patterns within the radius-based neighborhoods of a cell type, pooling the
+// neighborhoods of all selected FOVs.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py#L219
+export async function multiFindFpDist(multi, params) {
+    const { ct, datasetClass, maxDist = 20, minSize = 0, minSupport = 0.5, ifMax = true } = params;
+    assertCellTypeInAnyFov(multi, ct);
+    const transactions = selectFovs(multi, datasetClass).flatMap(({ context }) => {
+        const points = centerQueryPoints(context, findCellIndicesOfType(context, ct));
+        return radiusTransactions(context, points, maxDist, minSize).transactions;
+    });
+    return mineFrequentPatterns(transactions, minSupport, ifMax);
+}
+function getFov(multi, datasetId) {
+    const index = multi.datasetIds.indexOf(datasetId);
+    if (index === -1) {
+        throw new Error(`Found no dataset with ID ${datasetId}.`);
+    }
+    return multi.contexts[index];
+}
+// Find frequent (maximal) patterns within the k-NN neighborhoods of a cell type in a single FOV.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py#L993
+export async function findFpKnnFov(multi, params) {
+    const { ct, datasetId, k = 30, minSupport = 0.5, maxDist = 20 } = params;
+    const context = getFov(multi, datasetId);
+    if (!context.labels.includes(ct))
+        return [];
+    return findFpKnnSingle(context, { ct, k, minSupport, maxDist });
+}
+// Find frequent (maximal) patterns within the radius-based neighborhoods of a cell type in a single FOV.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py#L1049
+export async function findFpDistFov(multi, params) {
+    const { ct, datasetId, maxDist = 20, minSize = 0, minSupport = 0.5 } = params;
+    const context = getFov(multi, datasetId);
+    if (!context.labels.includes(ct))
+        return [];
+    return findFpDistSingle(context, { ct, maxDist, minSize, minSupport });
+}
+// Normalize user-specified motifs against the labels of all FOVs, throwing if none remain.
+function normalizeMultiMotifs(multi, motifs) {
+    const filtered = normalizeMotifs(motifs, allLabels(multi));
+    if (filtered.length === 0) {
+        throw new Error("All cell types in motifs are missing in the cell type labels.");
+    }
+    return filtered;
+}
+function multiMotifEnrichment(fovs, ct, motifs, neighborhood, returnCellIds) {
+    const totals = motifs.map(() => ({ numCells: 0, numCenter: 0, numMotif: 0, numCenterMotif: 0 }));
+    const neighborIds = motifs.map(() => ({}));
+    const centerIds = motifs.map(() => ({}));
+    for (const { datasetId, context } of fovs) {
+        const counts = countMotifs(context, ct, motifs, neighborhood(context), returnCellIds);
+        counts.forEach((c, m) => {
+            totals[m].numCells += c.numCells;
+            totals[m].numCenter += c.numCenter;
+            totals[m].numMotif += c.numMotif;
+            totals[m].numCenterMotif += c.numCenterMotif;
+            if (returnCellIds && c.centerIndices.length > 0) {
+                neighborIds[m][datasetId] = c.neighborIndices.map(j => context.obsIndex[j]);
+                centerIds[m][datasetId] = c.centerIndices.map(i => context.obsIndex[i]);
+            }
+        });
+    }
+    const out = motifs.map((motif, m) => {
+        const { neighborIds: _n, centerIds: _c, ...result } = computeMotifEnrichment({ center: ct, motif, ...totals[m] });
+        return returnCellIds
+            ? { ...result, neighborIds: neighborIds[m], centerIds: centerIds[m] }
+            : result;
+    });
+    return applyFdrCorrection(out);
+}
+// Perform motif enrichment analysis using k-nearest neighbors in multiple FOVs.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py#L319
+export async function multiMotifEnrichmentKnn(multi, params) {
+    const { ct, datasetClass, k = 30, minSupport = 0.5, maxDist = 20, returnCellIds = false, mode = 'maximal' } = params;
+    const fovs = selectFovs(multi, datasetClass);
+    assertCellTypeInAnyFov(multi, ct);
+    assertEnrichmentMode(mode);
+    if (mode === 'nested' && params.motifs === undefined) {
+        return nestedMotifDescent({
+            testMotifs: motifs => multiMotifEnrichmentKnn(multi, { ...params, motifs, mode: 'maximal' }),
+            frequentPatterns: await multiFindFpKnn(multi, { ct, datasetClass, k, minSupport, maxDist, ifMax: false }),
+        });
+    }
+    const motifs = params.motifs === undefined
+        ? (await multiFindFpKnn(multi, { ct, datasetClass, k, minSupport, maxDist })).map(p => p.itemsets)
+        : normalizeMultiMotifs(multi, params.motifs);
+    return multiMotifEnrichment(fovs, ct, motifs, context => knnNeighborhood(context, k, maxDist), returnCellIds);
+}
+// Perform motif enrichment analysis within a radius-based neighborhood in multiple FOVs.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py#L581
+export async function multiMotifEnrichmentDist(multi, params) {
+    const { ct, datasetClass, maxDist = 20, minSize = 0, minSupport = 0.5, returnCellIds = false, mode = 'maximal' } = params;
+    const fovs = selectFovs(multi, datasetClass);
+    assertCellTypeInAnyFov(multi, ct);
+    assertEnrichmentMode(mode);
+    if (mode === 'nested' && params.motifs === undefined) {
+        return nestedMotifDescent({
+            testMotifs: motifs => multiMotifEnrichmentDist(multi, { ...params, motifs, mode: 'maximal' }),
+            frequentPatterns: await multiFindFpDist(multi, { ct, datasetClass, maxDist, minSize, minSupport, ifMax: false }),
+        });
+    }
+    const motifs = params.motifs === undefined
+        ? (await multiFindFpDist(multi, { ct, datasetClass, maxDist, minSize, minSupport })).map(p => p.itemsets)
+        : normalizeMultiMotifs(multi, params.motifs);
+    return multiMotifEnrichment(fovs, ct, motifs, context => radiusNeighborhood(context, maxDist), returnCellIds);
+}
+// Pool the motif composition over the selected FOVs.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py#L851
+function multiMotifComposition(multi, ct, motifsParam, datasetClass, neighborhood) {
+    const fovs = selectFovs(multi, datasetClass);
+    assertCellTypeInAnyFov(multi, ct);
+    const motifs = normalizeMotifList(motifsParam, allLabels(multi));
+    return fovs.flatMap(({ datasetId, context }) => {
+        const cinds = findCellIndicesOfType(context, ct);
+        const labelsUnique = new Set(context.labels);
+        // A motif with a cell type missing from this FOV has no motif-positive center here.
+        const active = motifs.filter(m => m.every(t => labelsUnique.has(t)));
+        if (cinds.length === 0 || active.length === 0)
+            return [];
+        return motifCompositionRows(context, ct, active, cinds, neighborhood(context))
+            .map(row => ({ datasetId, ...row }));
+    });
+}
+// Compute the composition of motif cell types in the k-NN neighborhoods of center cells across multiple FOVs.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py#L931
+export function multiMotifCompositionKnn(multi, params) {
+    const { ct, motifs, datasetClass, k = 30, maxDist = 20 } = params;
+    return multiMotifComposition(multi, ct, motifs, datasetClass, context => knnNeighborhood(context, k, maxDist));
+}
+// Compute the composition of motif cell types in the radius-based neighborhoods of center cells across multiple FOVs.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py#L888
+export function multiMotifCompositionDist(multi, params) {
+    const { ct, motifs, datasetClass, maxDist = 20 } = params;
+    return multiMotifComposition(multi, ct, motifs, datasetClass, context => radiusNeighborhood(context, maxDist));
+}
+// Normalize motifs as differential_analysis_motif_* does (no filtering of unknown cell types).
+function toDifferentialMotifs(motifs) {
+    if (typeof motifs === 'string')
+        return [[motifs]];
+    if (motifs.length > 0 && typeof motifs[0] === 'string')
+        return [motifs];
+    return motifs;
+}
+// Test every motif for a difference in support between the datasets of two classes.
+// Returns all tested motifs, unlike differentialAnalysisKnn/Dist which return only the significant ones.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_differential_pattern.py
+function differentialTests(multi, datasetClasses, ct, motifsParam, 
+// Support of each motif among the given center cells of a dataset.
+supportsInFov) {
+    const motifs = [];
+    const motifKeys = new Set();
+    for (const motif of toDifferentialMotifs(motifsParam)) {
+        const sorted = motif.toSorted();
+        const key = JSON.stringify(sorted);
+        if (!motifKeys.has(key)) {
+            motifKeys.add(key);
+            motifs.push(sorted);
+        }
+    }
+    const supports = motifs.map(() => Object.fromEntries(datasetClasses.map(c => [c, []])));
+    for (const datasetClass of datasetClasses) {
+        for (const { context } of selectFovs(multi, datasetClass)) {
+            const cinds = findCellIndicesOfType(context, ct);
+            const fovSupports = cinds.length === 0 ? motifs.map(() => 0) : supportsInFov(context, cinds, motifs);
+            fovSupports.forEach((s, m) => supports[m][datasetClass].push(s));
+        }
+    }
+    const [c0, c1] = datasetClasses;
+    const results = motifs.map((itemsets, m) => {
+        const group1 = supports[m][c0];
+        const group2 = supports[m][c1];
+        let pValue = 1.0;
+        let datasetClassHigherFrequency = 'neither';
+        if (group1.length > 0 && group2.length > 0) {
+            pValue = mannWhitneyU(group1, group2).pValue;
+            // Determine which class has higher frequency using the median rank.
+            const ranks = rankAverage([...group1, ...group2]);
+            const medianRank1 = median(ranks.slice(0, group1.length));
+            const medianRank2 = median(ranks.slice(group1.length));
+            datasetClassHigherFrequency = medianRank1 > medianRank2 ? c0 : c1;
+        }
+        return {
+            itemsets,
+            supports: supports[m],
+            supportMean: { [c0]: mean(group1), [c1]: mean(group2) },
+            pValue,
+            datasetClassHigherFrequency,
+        };
+    });
+    if (results.length > 1) {
+        const { rejected, adjusted } = fdrCorrection(results.map(r => r.pValue), 0.05);
+        return results.map((r, i) => ({ ...r, adjPValue: adjusted[i], ifSignificant: rejected[i] }));
+    }
+    return results.map(r => ({ ...r, adjPValue: r.pValue, ifSignificant: r.pValue < 0.05 }));
+}
+// Split the significant results by the class with the higher frequency, sorted by adjusted p-value.
+function splitSignificant(results, datasetClasses) {
+    return Object.fromEntries(datasetClasses.map(c => [
+        c,
+        results
+            .filter(r => r.datasetClassHigherFrequency === c && r.ifSignificant)
+            .map(({ itemsets, supportMean, adjPValue }) => ({ itemsets, supportMean, adjPValue }))
+            .toSorted((a, b) => a.adjPValue - b.adjPValue),
+    ]));
+}
+// Union of the frequent patterns discovered in each dataset of the two classes.
+async function discoverMotifs(multi, datasetClasses, findFpFov) {
+    const motifs = new Map();
+    for (const datasetClass of datasetClasses) {
+        for (const { datasetId } of selectFovs(multi, datasetClass)) {
+            for (const { itemsets } of await findFpFov(datasetId)) {
+                motifs.set(JSON.stringify(itemsets.toSorted()), itemsets.toSorted());
+            }
+        }
+    }
+    return Array.from(motifs.values());
+}
+function validateDifferentialClasses(multi, datasetClasses) {
+    if (datasetClasses.length !== 2) {
+        throw new Error("Require 2 dataset classes for differential analysis.");
+    }
+    selectFovs(multi, datasetClasses);
+}
+// Fraction of the center cells whose neighborhood contains every motif cell type
+// (0 for motifs with a cell type missing from the dataset).
+function motifSupports(context, cinds, motifs, neighborsOf, isValidCenter = () => true) {
+    const labelsUnique = new Set(context.labels);
+    const neighborTypes = cinds.map((i) => {
+        const neighbors = neighborsOf(i);
+        return isValidCenter(neighbors) ? new Set(neighbors.map(j => context.labels[j])) : null;
+    });
+    return motifs.map((motif) => {
+        if (!motif.every(t => labelsUnique.has(t)))
+            return 0;
+        const count = neighborTypes.filter(types => types !== null && motif.every(t => types.has(t))).length;
+        return count / cinds.length;
+    });
+}
+// Test all motifs for differential support between two dataset classes using k-NN neighborhoods.
+// Returns every tested motif (including non-significant ones).
+export async function differentialTestsKnn(multi, params) {
+    const { ct, datasetClasses, k = 30, minSupport = 0.5, maxDist = 20 } = params;
+    validateDifferentialClasses(multi, datasetClasses);
+    const motifs = params.motifs ?? await discoverMotifs(multi, datasetClasses, datasetId => (findFpKnnFov(multi, { ct, datasetId, k, minSupport, maxDist })));
+    return differentialTests(multi, datasetClasses, ct, motifs, (context, cinds, ms) => (motifSupports(context, cinds, ms, knnNeighborhood(context, k, maxDist))));
+}
+// Perform differential analysis of motif patterns between two dataset classes using k-NN neighborhoods.
+// Returns, for each class, the motifs significantly more frequent in that class.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py#L1105
+export async function differentialAnalysisKnn(multi, params) {
+    return splitSignificant(await differentialTestsKnn(multi, params), params.datasetClasses);
+}
+// Test all motifs for differential support between two dataset classes using radius-based neighborhoods.
+// Returns every tested motif (including non-significant ones).
+export async function differentialTestsDist(multi, params) {
+    const { ct, datasetClasses, maxDist = 20, minSupport = 0.5, minSize = 0 } = params;
+    validateDifferentialClasses(multi, datasetClasses);
+    const motifs = params.motifs ?? await discoverMotifs(multi, datasetClasses, datasetId => (findFpDistFov(multi, { ct, datasetId, maxDist, minSize, minSupport })));
+    // Center cells with neighborhoods not larger than minSize never count as having the motif,
+    // but still count in the denominator of the support.
+    return differentialTests(multi, datasetClasses, ct, motifs, (context, cinds, ms) => (motifSupports(context, cinds, ms, radiusNeighborhood(context, maxDist), neighbors => neighbors.length > minSize)));
+}
+// Perform differential analysis of motif patterns between two dataset classes using radius-based neighborhoods.
+// Returns, for each class, the motifs significantly more frequent in that class.
+// Reference: https://github.com/ShaokunAn/Spatial-Query/blob/9250b61/SpatialQuery/spatial_query_multiple_fov.py#L1206
+export async function differentialAnalysisDist(multi, params) {
+    return splitSignificant(await differentialTestsDist(multi, params), params.datasetClasses);
+}
+//# sourceMappingURL=multi-fov.js.map

package/dist/multi-fov.js.map

@@ -0,0 +1 @@
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package/dist/nested.d.ts

@@ -0,0 +1,17 @@
+import { type FrequentPattern } from './fpgrowth.js';
+type TestedMotif = {
+    motifs: string[];
+    pValue: number;
+    adjPValue?: number;
+    ifSignificant?: boolean;
+};
+type NestedMotifDescentParams<T> = {
+    testMotifs: (motifs: string[][]) => Promise<T[]>;
+    frequentPatterns: FrequentPattern[];
+    supportTol?: number;
+    maxTestedPatterns?: number;
+    maxExpansionFactor?: number;
+};
+export declare function nestedMotifDescent<T extends TestedMotif>(params: NestedMotifDescentParams<T>): Promise<T[]>;
+export {};
+//# sourceMappingURL=nested.d.ts.map

package/dist/nested.d.ts.map

@@ -0,0 +1 @@
+{"version":3,"file":"nested.d.ts","sourceRoot":"","sources":["../src/nested.ts"],"names":[],"mappings":"AACA,OAAO,EAAuB,KAAK,eAAe,EAAE,MAAM,eAAe,CAAC;AA4B1E,KAAK,WAAW,GAAG;IAAE,MAAM,EAAE,MAAM,EAAE,CAAC;IAAC,MAAM,EAAE,MAAM,CAAC;IAAC,SAAS,CAAC,EAAE,MAAM,CAAC;IAAC,aAAa,CAAC,EAAE,OAAO,CAAA;CAAE,CAAC;AAKrG,KAAK,wBAAwB,CAAC,CAAC,IAAI;IAGjC,UAAU,EAAE,CAAC,MAAM,EAAE,MAAM,EAAE,EAAE,KAAK,OAAO,CAAC,CAAC,EAAE,CAAC,CAAC;IAGjD,gBAAgB,EAAE,eAAe,EAAE,CAAC;IAEpC,UAAU,CAAC,EAAE,MAAM,CAAC;IAEpB,iBAAiB,CAAC,EAAE,MAAM,CAAC;IAC3B,kBAAkB,CAAC,EAAE,MAAM,CAAC;CAC7B,CAAC;AAIF,wBAAsB,kBAAkB,CAAC,CAAC,SAAS,WAAW,EAAE,MAAM,EAAE,wBAAwB,CAAC,CAAC,CAAC,GAAG,OAAO,CAAC,CAAC,EAAE,CAAC,CAwFjH"}