diff --git a/client/src/components/Collections/PairedListCollectionCreator.vue b/client/src/components/Collections/PairedListCollectionCreator.vue
index ba46d2139934..8ae36377742a 100644
--- a/client/src/components/Collections/PairedListCollectionCreator.vue
+++ b/client/src/components/Collections/PairedListCollectionCreator.vue
@@ -93,6 +93,14 @@ const hasFilter = computed(() => forwardFilter.value || reverseFilter.value);
 const strategy = ref(autoPairLCS);
 const duplicatePairNames = ref<string[]>([]);
 
+const canClearFilters = computed(() => {
+    return forwardFilter.value || reverseFilter.value;
+});
+
+const canAutoPair = computed(() => {
+    return forwardFilter.value && reverseFilter.value && pairableElements.value.length > 0;
+});
+
 const forwardElements = computed<HDASummary[]>(() => {
     return filterElements(workingElements.value, forwardFilter.value);
 });
@@ -117,7 +125,11 @@ const autoPairButton = computed(() => {
     let variant;
     let icon;
     let text;
-    if (!firstAutoPairDone.value && pairableElements.value.length > 0) {
+    if (!canAutoPair.value) {
+        variant = "secondary";
+        icon = faLink;
+        text = localize("Specify simple filters to divide datasets into forward and reverse reads for pairing.");
+    } else if (!firstAutoPairDone.value && pairableElements.value.length > 0) {
         variant = "primary";
         icon = faExclamationCircle;
         text = localize("Click to auto-pair datasets based on the current filters");
@@ -235,8 +247,11 @@ function initialFiltersSet() {
             illumina++;
         }
     });
-
-    if (illumina > dot12s && illumina > Rs) {
+    // if we cannot filter don't set an initial filter and hide all the data
+    if (illumina == 0 && dot12s == 0 && Rs == 0) {
+        forwardFilter.value = "";
+        reverseFilter.value = "";
+    } else if (illumina > dot12s && illumina > Rs) {
         changeFilters("illumina");
     } else if (dot12s > illumina && dot12s > Rs) {
         changeFilters("dot12s");
@@ -1133,6 +1148,7 @@ function _naiveStartingAndEndingLCS(s1: string, s2: string) {
                                         <BButtonGroup vertical>
                                             <BButton
                                                 class="clear-filters-link"
+                                                :disabled="!canClearFilters"
                                                 size="sm"
                                                 :variant="hasFilter ? 'danger' : 'secondary'"
                                                 @click="clickClearFilters">
@@ -1141,6 +1157,7 @@ function _naiveStartingAndEndingLCS(s1: string, s2: string) {
                                             </BButton>
                                             <BButton
                                                 class="autopair-link"
+                                                :disabled="!canAutoPair"
                                                 size="sm"
                                                 :title="autoPairButton.text"
                                                 :variant="autoPairButton.variant"
@@ -1309,6 +1326,8 @@ $fa-font-path: "../../../node_modules/@fortawesome/fontawesome-free/webfonts/";
 @import "~@fortawesome/fontawesome-free/scss/solid";
 @import "~@fortawesome/fontawesome-free/scss/fontawesome";
 @import "~@fortawesome/fontawesome-free/scss/brands";
+@import "~bootstrap/scss/_functions.scss";
+@import "theme/blue.scss";
 .paired-column {
     text-align: center;
     // mess with these two to make center more/scss priority
@@ -1355,7 +1374,7 @@ li.dataset.paired {
             white-space: nowrap;
             overflow: hidden;
             border: 2px solid grey;
-            background: #aff1af;
+            background: $state-success-bg;
             text-align: center;
             span {
                 display: inline-block;
diff --git a/lib/galaxy/selenium/navigates_galaxy.py b/lib/galaxy/selenium/navigates_galaxy.py
index 141d6e1c28ec..bccafc32e933 100644
--- a/lib/galaxy/selenium/navigates_galaxy.py
+++ b/lib/galaxy/selenium/navigates_galaxy.py
@@ -914,8 +914,7 @@ def upload_paired_list(self, test_paths, name="test", ext=None, genome=None, hid
         if not hide_source_items:
             self.collection_builder_hide_originals()
 
-        self.collection_builder_clear_filters()
-        # TODO: generalize and loop these clicks so we don't need the assert
+        self.ensure_collection_builder_filters_cleared()
         assert len(test_paths) == 2
         self.collection_builder_click_paired_item("forward", 0)
         self.collection_builder_click_paired_item("reverse", 1)
@@ -2053,8 +2052,15 @@ def collection_builder_hide_originals(self):
     def collection_builder_create(self):
         self.wait_for_and_click_selector("button.create-collection")
 
+    def ensure_collection_builder_filters_cleared(self):
+        clear_filters = self.components.collection_builders.clear_filters
+        element = clear_filters.wait_for_present()
+        if "disabled" not in element.get_attribute("class").split(" "):
+            self.collection_builder_clear_filters()
+
     def collection_builder_clear_filters(self):
-        self.wait_for_and_click_selector("button.clear-filters-link")
+        clear_filters = self.components.collection_builders.clear_filters
+        clear_filters.wait_for_and_click()
 
     def collection_builder_click_paired_item(self, forward_or_reverse, item):
         assert forward_or_reverse in ["forward", "reverse"]
diff --git a/lib/galaxy_test/selenium/test_collection_builders.py b/lib/galaxy_test/selenium/test_collection_builders.py
index 24b47a825cf3..2c57e632e8b5 100644
--- a/lib/galaxy_test/selenium/test_collection_builders.py
+++ b/lib/galaxy_test/selenium/test_collection_builders.py
@@ -39,7 +39,6 @@ def test_build_paired_list_simple(self):
         self.perform_upload(self.get_filename("2.tabular"))
         self._wait_for_and_select([1, 2])
         self._collection_dropdown("build list of pairs")
-        self.collection_builder_clear_filters()
         self.collection_builder_click_paired_item("forward", 0)
         self.collection_builder_click_paired_item("reverse", 1)
         self.collection_builder_set_name("my awesome paired list")
@@ -61,7 +60,7 @@ def test_build_paired_list_show_original(self):
         self._wait_for_and_select([1, 2])
         self._collection_dropdown("build list of pairs")
         collection_builders = self.components.collection_builders
-        collection_builders.clear_filters.wait_for_and_click()
+        self.ensure_collection_builder_filters_cleared()
         forward_column = collection_builders.forward_datasets.wait_for_visible()
         first_datset_forward = forward_column.find_elements(self.by.CSS_SELECTOR, "li")[0]
         first_datset_forward.click()