diff --git a/webapp/TargetedMS/js/QCPlotHelperBase.js b/webapp/TargetedMS/js/QCPlotHelperBase.js
index 935e91b88..652739377 100644
--- a/webapp/TargetedMS/js/QCPlotHelperBase.js
+++ b/webapp/TargetedMS/js/QCPlotHelperBase.js
@@ -694,7 +694,7 @@ Ext4.define("LABKEY.targetedms.QCPlotHelperBase", {
         return precursor;
     },
 
-    addEachCombinedPrecursorPlot: function(plotIndex, id, combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, plotType, isCUSUMMean) {
+    addEachCombinedPrecursorPlot: function(plotIndex, id, combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, plotType, isCUSUMMean, scope) {
         let plotLegendData = this.getCombinedPlotLegendData(metricProps, groupColors, yAxisCount, plotType, isCUSUMMean);
 
         if (plotType !== LABKEY.vis.TrendingLinePlotType.CUSUM) {
@@ -794,6 +794,24 @@ Ext4.define("LABKEY.targetedms.QCPlotHelperBase", {
                     visibility: this.isMultiSeries() ? undefined : 'hidden'
                 }
             },
+            brushing: !this.allowGuideSetBrushing() ? undefined : {
+                dimension: 'x',
+                fillOpacity: 0.4,
+                fillColor: 'rgba(20, 204, 201, 1)',
+                strokeColor: 'rgba(20, 204, 201, 1)',
+                brushstart: function(event, data, extent, plot, layerSelections) {
+                    scope.plotBrushStartEvent(plot);
+                },
+                brush: function(event, data, extent, plot, layerSelections) {
+                    scope.plotBrushEvent(extent, plot, layerSelections);
+                },
+                brushend: function(event, data, extent, plot, layerSelections) {
+                    scope.plotBrushEndEvent(data[data.length - 1], extent, plot);
+                },
+                brushclear: function(event, data, plot, layerSelections) {
+                    scope.plotBrushClearEvent(data[data.length - 1], plot);
+                }
+            },
             properties: trendLineProps
         });
 
diff --git a/webapp/TargetedMS/js/QCPlotHelperWrapper.js b/webapp/TargetedMS/js/QCPlotHelperWrapper.js
index 0178168c7..686efef74 100644
--- a/webapp/TargetedMS/js/QCPlotHelperWrapper.js
+++ b/webapp/TargetedMS/js/QCPlotHelperWrapper.js
@@ -128,6 +128,7 @@ Ext4.define("LABKEY.targetedms.QCPlotHelperWrapper", {
     },
 
     addCombinedPeptideSinglePlot : function(metricProps) {
+        const me = this; // for plot brushing
         let     yAxisCount = this.isMultiSeries() ? 2 : 1, //Will only have a right if there is already a left y-axis
                 groupColors = this.getColorRange(),
                 combinePlotData = this.getCombinedPlotInitData(),
@@ -195,25 +196,25 @@ Ext4.define("LABKEY.targetedms.QCPlotHelperWrapper", {
             legendMargin = 300;
 
         if (this.showMetricValuePlot()) {
-            this.addEachCombinedPrecursorPlot(plotIndex, ids[plotIndex++], combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, LABKEY.vis.TrendingLinePlotType.LeveyJennings);
+            this.addEachCombinedPrecursorPlot(plotIndex, ids[plotIndex++], combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, LABKEY.vis.TrendingLinePlotType.LeveyJennings, false, me);
         }
         if (this.showMovingRangePlot()) {
-            this.addEachCombinedPrecursorPlot(plotIndex, ids[plotIndex++], combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, LABKEY.vis.TrendingLinePlotType.MovingRange);
+            this.addEachCombinedPrecursorPlot(plotIndex, ids[plotIndex++], combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, LABKEY.vis.TrendingLinePlotType.MovingRange, false, me);
         }
         if (this.showMeanCUSUMPlot()) {
-            this.addEachCombinedPrecursorPlot(plotIndex, ids[plotIndex++], combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, LABKEY.vis.TrendingLinePlotType.CUSUM, true);
+            this.addEachCombinedPrecursorPlot(plotIndex, ids[plotIndex++], combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, LABKEY.vis.TrendingLinePlotType.CUSUM, true, me);
         }
         if (this.showVariableCUSUMPlot()) {
-            this.addEachCombinedPrecursorPlot(plotIndex, ids[plotIndex], combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, LABKEY.vis.TrendingLinePlotType.CUSUM, false);
+            this.addEachCombinedPrecursorPlot(plotIndex, ids[plotIndex], combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, LABKEY.vis.TrendingLinePlotType.CUSUM, false, me);
         }
         if (this.showTrailingMeanPlot()) {
-            this.addEachCombinedPrecursorPlot(plotIndex, ids[plotIndex], combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, LABKEY.vis.TrendingLinePlotType.TrailingMean, false);
+            this.addEachCombinedPrecursorPlot(plotIndex, ids[plotIndex], combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, LABKEY.vis.TrendingLinePlotType.TrailingMean, false, me);
         }
         if (this.showTrailingCVPlot()) {
-            this.addEachCombinedPrecursorPlot(plotIndex, ids[plotIndex], combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, LABKEY.vis.TrendingLinePlotType.TrailingCV, false);
+            this.addEachCombinedPrecursorPlot(plotIndex, ids[plotIndex], combinePlotData, groupColors, yAxisCount, metricProps, showLogInvalid, legendMargin, LABKEY.vis.TrendingLinePlotType.TrailingCV, false, me);
         }
 
-
+        this.setPlotBrushingDisplayStyle();
         return true;
     },
 
diff --git a/webapp/TargetedMS/js/QCTrendPlotPanel.js b/webapp/TargetedMS/js/QCTrendPlotPanel.js
index 16b5e3aae..89489a698 100644
--- a/webapp/TargetedMS/js/QCTrendPlotPanel.js
+++ b/webapp/TargetedMS/js/QCTrendPlotPanel.js
@@ -1169,7 +1169,7 @@ Ext4.define('LABKEY.targetedms.QCTrendPlotPanel', {
         if (!this.createGuideSetToggleButton) {
             this.createGuideSetToggleButton = Ext4.create('Ext.button.Button', {
                 text: 'Create Guide Set',
-                tooltip: 'Enable/disable guide set creation mode. Supported for separate plots, not grouped by date, when ' + LABKEY.targetedms.QCPlotHelperBase.maxPointsPerSeries + ' or fewer samples are shown',
+                tooltip: 'Enable/disable guide set creation mode. Supported for plots, when ' + LABKEY.targetedms.QCPlotHelperBase.maxPointsPerSeries + ' or fewer samples are shown',
                 disabled: !this.canCreateGuideSetFromPlot(),
                 enableToggle: true,
                 handler: function(btn) {
@@ -1183,11 +1183,11 @@ Ext4.define('LABKEY.targetedms.QCTrendPlotPanel', {
     },
 
     canCreateGuideSetFromPlot : function() {
-        return !(this.groupedX || this.singlePlot || this.isMultiSeries() || this.showExpRunRange || !this.showDataPoints);
+        return !(this.showExpRunRange || !this.showDataPoints);
     },
 
     setBrushingEnabled : function(enabled) {
-        // we don't currently allow creation of guide sets in single plot mode, grouped x-axis mode, multi series mode or when showingExpRunRange
+        // we don't currently allow creation when showingExpRunRange
         this.getGuideSetCreateButton().setDisabled(!this.canCreateGuideSetFromPlot());
 
         this.enableBrushing = enabled;
@@ -1552,7 +1552,7 @@ Ext4.define('LABKEY.targetedms.QCTrendPlotPanel', {
         this.bringSvgElementToFront(plot, "g.guideset-svg-button");
     },
 
-    plotBrushClearEvent : function(data, plot) {
+    plotBrushClearEvent : function() {
         this.plotBrushSelection = undefined;
     },
 
@@ -1561,7 +1561,7 @@ Ext4.define('LABKEY.targetedms.QCTrendPlotPanel', {
     },
 
     allowGuideSetBrushing : function() {
-        return this.canUserEdit() && !this.groupedX;
+        return this.canUserEdit();
     },
 
     createGuideSetSvgButton : function(plot, text, xLeftPos, width) {
@@ -1586,8 +1586,9 @@ Ext4.define('LABKEY.targetedms.QCTrendPlotPanel', {
     setPlotBrushingDisplayStyle : function() {
         // hide the brushing related components for all plots if not in "create guide set" mode
         var displayStyle = this.enableBrushing ? 'inline' : 'none';
-        d3.selectAll('.brush').style({'display': displayStyle});
-        d3.selectAll('.x-axis-handle').style({'display': displayStyle});
+        // Scope the selection to only plots within the current plotDivId to avoid affecting other plot types
+        d3.select('#' + this.plotDivId).selectAll('.brush').style({'display': displayStyle});
+        d3.select('#' + this.plotDivId).selectAll('.x-axis-handle').style({'display': displayStyle});
     },
 
     clearPlotBrush : function(plot) {