@sjcrh/proteinpaint-server 2.184.0 → 2.185.0

package/routes/termdb.proteome.js

@@ -51,9 +51,10 @@ function init({ genomes }) {
             __abortSignal: q.__abortSignal
           });
           const controlSampleIds = cohortData.controlSampleIds || /* @__PURE__ */ new Set();
+          const prior = assay.cohorts[cohortName].prior;
           for (const entry of cohortData.allEntries || []) {
             const s2v = entry.s2v;
-            const stats = getCohortStats(s2v, controlSampleIds);
+            const stats = getCohortStats(s2v, controlSampleIds, prior);
             delete entry.s2v;
             entry.foldChange = stats.foldChange;
             entry.pValue = stats.pValue;
@@ -71,7 +72,7 @@ function init({ genomes }) {
     }
   };
 }
-function getCohortStats(allS2v, controlSampleIds) {
+function getCohortStats(allS2v, controlSampleIds, prior) {
   if (!allS2v || typeof allS2v != "object") return { foldChange: null, pValue: null, testedN: 0, controlN: 0 };
   const controlValues = [];
   const testedValues = [];
@@ -84,7 +85,10 @@ function getCohortStats(allS2v, controlSampleIds) {
   const controlMean = controlValues?.length ? controlValues.reduce((sum, v) => sum + v, 0) / controlValues.length : null;
   const testedMean = testedValues?.length ? testedValues.reduce((sum, v) => sum + v, 0) / testedValues.length : null;
   const foldChange = testedMean != null && controlMean != null && Number.isFinite(testedMean) && Number.isFinite(controlMean) && controlMean !== 0 ? testedMean / controlMean : null;
-  const pValue = getWelchPValue(testedValues, controlValues);
+  if (!Number.isFinite(prior?.d0) || prior.d0 <= 0 || !Number.isFinite(prior?.s0sq) || prior.s0sq <= 0) {
+    throw "prior with finite positive d0 and s0sq is required for moderated t-test";
+  }
+  const pValue = getModeratedPValue(testedValues, controlValues, prior);
   return {
     foldChange,
     pValue,
@@ -92,36 +96,38 @@ function getCohortStats(allS2v, controlSampleIds) {
     controlN: controlValues.length
   };
 }
-function getWelchPValue(a, b) {
+function getModeratedPValue(a, b, prior) {
   const n1 = a.length;
   const n2 = b.length;
   if (n1 < 2 || n2 < 2) return null;
   const mean1 = a.reduce((s, v) => s + v, 0) / n1;
   const mean2 = b.reduce((s, v) => s + v, 0) / n2;
-  const var1 = sampleVariance(a, mean1);
-  const var2 = sampleVariance(b, mean2);
-  if (!Number.isFinite(var1) || !Number.isFinite(var2)) return null;
-  const se2 = var1 / n1 + var2 / n2;
-  if (!(se2 > 0)) {
+  let ss1 = 0;
+  for (const v of a) {
+    const d = v - mean1;
+    ss1 += d * d;
+  }
+  let ss2 = 0;
+  for (const v of b) {
+    const d = v - mean2;
+    ss2 += d * d;
+  }
+  const dfResidual = n1 + n2 - 2;
+  const pooledVar = (ss1 + ss2) / dfResidual;
+  const { d0, s0sq } = prior;
+  const sTildeSq = (d0 * s0sq + dfResidual * pooledVar) / (d0 + dfResidual);
+  const se = Math.sqrt(sTildeSq * (1 / n1 + 1 / n2));
+  if (!(se > 0)) {
     if (mean1 === mean2) return 1;
     return 1e-300;
   }
-  const t = (mean1 - mean2) / Math.sqrt(se2);
-  const df = se2 * se2 / ((var1 / n1) ** 2 / (n1 - 1) + (var2 / n2) ** 2 / (n2 - 1));
+  const t = (mean1 - mean2) / se;
+  const df = d0 + dfResidual;
   if (!Number.isFinite(df) || df < 0.1) return null;
   const p = 2 * tCdfTail(Math.abs(t), df);
   if (!Number.isFinite(p)) return null;
   return Math.max(1e-300, Math.min(1, p));
 }
-function sampleVariance(lst, mean) {
-  if (lst.length < 2) return NaN;
-  let sumsq = 0;
-  for (const v of lst) {
-    const d = v - mean;
-    sumsq += d * d;
-  }
-  return sumsq / (lst.length - 1);
-}
 function tCdfTail(t, df) {
   const x = df / (df + t * t);
   return 0.5 * regularizedBetaIncomplete(df / 2, 0.5, x);
@@ -217,6 +223,8 @@ async function validate_query_proteome(ds) {
         if (!cohort.controlFilter)
           throw `Missing controlFilter in queries.proteome.assays.${assayName}.cohorts.${cohortName}`;
         if (!cohort.caseFilter) throw `Missing caseFilter in queries.proteome.assays.${assayName}.cohorts.${cohortName}`;
+        if (!cohort.prior?.d0 || !cohort.prior?.s0sq)
+          throw `Missing prior.d0 and prior.s0sq in queries.proteome.assays.${assayName}.cohorts.${cohortName}`;
       }
     } else {
       throw `Invalid assay structure for "${assayName}". Must have .cohorts`;

package/routes/termdb.singlecellDEgenes.js

@@ -25,7 +25,8 @@ function init({ genomes }) {
       if (!ds.queries?.singleCell?.DEgenes || !ds.queries.singleCell.DEgenes.get)
         throw new Error("DE genes not supported on this dataset.");
       result = await ds.queries.singleCell.DEgenes.get(q);
-      if (!result || !result.data || !result?.data?.length) {
+      const isEmpty = !result || !result.data || (Array.isArray(result.data) ? result.data.length === 0 : !result.data.totalRows);
+      if (isEmpty) {
         result = {
           status: 404,
           error: !result ? "No data found." : "No differentially expressed genes found."

package/routes/termdb.singlecellSamples.js

@@ -48,11 +48,11 @@ async function validate_query_singleCell(ds, genome) {
   const q = ds.queries.singleCell;
   if (!q) return;
   if (typeof q.samples != "object") throw new Error("singleCell.samples{} not object");
+  if (typeof q.data != "object") throw new Error("singleCell.data{} not object");
   if (typeof q.samples.get == "function") {
   } else {
-    await validateSamplesNative(q.samples, q.data, ds);
+    await validateSamples(q, ds);
   }
-  if (typeof q.data != "object") throw new Error("singleCell.data{} not object");
   if (q.data.src == "gdcapi") {
     gdc_validate_query_singleCell_data(ds, genome);
   } else if (q.data.src == "native") {
@@ -85,7 +85,8 @@ function validateImages(images) {
   if (!images.label) images.label = "Images";
   if (!images.fileName) throw new Error("images.fileName missing");
 }
-async function validateSamplesNative(S, D, ds) {
+async function validateSamples(q, ds) {
+  const S = q.samples, D = q.data;
   const samples = /* @__PURE__ */ new Map();
   for (const plot of D.plots) {
     for (const fn of await fs.promises.readdir(path.join(serverconfig.tpmasterdir, plot.folder))) {
@@ -102,6 +103,8 @@ async function validateSamplesNative(S, D, ds) {
     }
     if (!plot.colorColumns || plot.colorColumns.length == 0) continue;
   }
+  if (samples.size == 0) throw new Error("no scrna samples found");
+  console.log(samples.size, "singleCell samples loaded from " + ds.label);
   if (S.sampleColumns) {
     for (const { termid } of S.sampleColumns) {
       const term = ds.cohort.termdb.q.termjsonByOneid(termid);
@@ -114,7 +117,13 @@ async function validateSamplesNative(S, D, ds) {
     }
   }
   S.get = () => {
-    return { samples: [...samples.values()] };
+    const re = { samples: [...samples.values()] };
+    if (q.metaResults) {
+      re.metaResults = q.metaResults.map((i) => {
+        return { name: i.name };
+      });
+    }
+    return re;
   };
 }
 function validateDataNative(D, ds) {
@@ -126,6 +135,28 @@ function validateDataNative(D, ds) {
   }
   const file2Lines = {};
   D.get = async (q) => {
+    if (q.checkPlotAvailability) {
+      const plots2 = [];
+      for (const plot of D.plots) {
+        if (!q.plots.includes(plot.name)) continue;
+        const tsvfile = path.join(
+          serverconfig.tpmasterdir,
+          plot.folder,
+          (q.sample?.eID || q.sample?.sID) + (plot.fileSuffix || "")
+        );
+        try {
+          await file_is_readable(tsvfile);
+          plots2.push({
+            name: plot.name,
+            expCells: [],
+            // FIXME avoid breaking client but shouldn't be needed
+            noExpCells: []
+          });
+        } catch (_) {
+        }
+      }
+      return { plots: plots2 };
+    }
     const plots = [];
     let geneExpMap;
     if (ds.queries.singleCell.geneExpression && q.gene) {
@@ -138,7 +169,7 @@ function validateDataNative(D, ds) {
       const tsvfile = path.join(
         serverconfig.tpmasterdir,
         plot.folder,
-        (q.sample?.eID || q.sample?.sID) + plot.fileSuffix
+        (q.sample?.eID || q.sample?.sID) + (plot.fileSuffix || "")
       );
       if (!file2Lines[tsvfile]) {
         await file_is_readable(tsvfile);