diff --git a/client/src/components/Collections/pairing.ts b/client/src/components/Collections/pairing.ts
index 351aab5288eb..872fd2bfff12 100644
--- a/client/src/components/Collections/pairing.ts
+++ b/client/src/components/Collections/pairing.ts
@@ -3,6 +3,7 @@ import type { GenericPair } from "@/components/Collections/common/buildCollectio
 export const COMMON_FILTERS = {
     illumina: ["_1", "_2"] as [string, string],
     Rs: ["_R1", "_R2"] as [string, string],
+    Fs: ["_F", "_R"] as [string, string],
     dot12s: [".1.fastq", ".2.fastq"] as [string, string],
 };
 export type CommonFiltersType = keyof typeof COMMON_FILTERS;
@@ -16,6 +17,7 @@ export function guessInitialFilterType(elements: HasName[]): CommonFiltersType |
     let illumina = 0;
     let dot12s = 0;
     let Rs = 0;
+    let Fs = 0;
 
     //should we limit the forEach? What if there are 1000s of elements?
     elements.forEach((element) => {
@@ -23,19 +25,23 @@ export function guessInitialFilterType(elements: HasName[]): CommonFiltersType |
             dot12s++;
         } else if (element.name?.includes("_R1") || element.name?.includes("_R2")) {
             Rs++;
+        } else if (element.name?.includes("_F") || element.name?.includes("_R")) {
+            Fs++;
         } else if (element.name?.includes("_1") || element.name?.includes("_2")) {
             illumina++;
         }
     });
     // if we cannot filter don't set an initial filter and hide all the data
-    if (illumina === 0 && dot12s === 0 && Rs === 0) {
+    if (illumina === 0 && dot12s === 0 && Rs === 0 && Fs === 0) {
         return null;
-    } else if (illumina > dot12s && illumina > Rs) {
+    } else if (illumina > dot12s && illumina > Rs && illumina > Fs) {
         return "illumina";
-    } else if (dot12s > illumina && dot12s > Rs) {
+    } else if (dot12s > illumina && dot12s > Rs && dot12s > Fs) {
         return "dot12s";
-    } else if (Rs > illumina && Rs > dot12s) {
+    } else if (Rs > illumina && Rs > dot12s && Rs > Fs) {
         return "Rs";
+    } else if (Fs > illumina && Fs > dot12s && Fs > Rs) {
+        return "Fs";
     } else {
         return "illumina";
     }
diff --git a/lib/galaxy/model/dataset_collections/auto_pairing.py b/lib/galaxy/model/dataset_collections/auto_pairing.py
index 351c4657e52c..7433bb07e3d9 100644
--- a/lib/galaxy/model/dataset_collections/auto_pairing.py
+++ b/lib/galaxy/model/dataset_collections/auto_pairing.py
@@ -20,6 +20,7 @@ class HasName(Protocol):
 COMMON_FILTERS: dict[str, tuple[str, str]] = {
     "illumina": ("_1", "_2"),
     "Rs": ("_R1", "_R2"),
+    "Fs": ("_F", "_R"),
     "dot12s": (".1.fastq", ".2.fastq"),
 }
 
@@ -116,25 +117,32 @@ def guess_initial_filter_type(elements: list[T]) -> Optional[str]:
     illumina = 0
     dot12s = 0
     Rs = 0
+    Fs = 0
 
     # Iterate through elements and count occurrences of filter patterns
+    # Order matters: more specific patterns must be checked before less specific ones
+    # (_R1/_R2 before _F/_R since _R is a substring of _R1)
     for element in elements:
         if ".1.fastq" in element.name or ".2.fastq" in element.name:
             dot12s += 1
         elif "_R1" in element.name or "_R2" in element.name:
             Rs += 1
+        elif "_F" in element.name or "_R" in element.name:
+            Fs += 1
         elif "_1" in element.name or "_2" in element.name:
             illumina += 1
 
     # Determine the most likely filter type
-    if illumina == 0 and dot12s == 0 and Rs == 0:
+    if illumina == 0 and dot12s == 0 and Rs == 0 and Fs == 0:
         return None
-    elif illumina > dot12s and illumina > Rs:
+    elif illumina > dot12s and illumina > Rs and illumina > Fs:
         return "illumina"
-    elif dot12s > illumina and dot12s > Rs:
+    elif dot12s > illumina and dot12s > Rs and dot12s > Fs:
         return "dot12s"
-    elif Rs > illumina and Rs > dot12s:
+    elif Rs > illumina and Rs > dot12s and Rs > Fs:
         return "Rs"
+    elif Fs > illumina and Fs > dot12s and Fs > Rs:
+        return "Fs"
     else:
         return "illumina"
 
diff --git a/lib/galaxy/model/dataset_collections/auto_pairing_spec.yml b/lib/galaxy/model/dataset_collections/auto_pairing_spec.yml
index 8b81d649abc8..f0dc8615a17c 100644
--- a/lib/galaxy/model/dataset_collections/auto_pairing_spec.yml
+++ b/lib/galaxy/model/dataset_collections/auto_pairing_spec.yml
@@ -74,3 +74,35 @@
     input:
       forward: input_1.fastq.bz2
       reverse: input_2.fastq.bz2
+
+- doc: Simple _F/_R split.
+  inputs:
+  - input_F.fastq
+  - input_R.fastq
+  paired:
+    input:
+      forward: input_F.fastq
+      reverse: input_R.fastq
+
+- doc: Compressed _F/_R split (.gz).
+  inputs:
+  - ERR042228_F.fq.gz
+  - ERR042228_R.fq.gz
+  paired:
+    ERR042228:
+      forward: ERR042228_F.fq.gz
+      reverse: ERR042228_R.fq.gz
+
+- doc: Multiple _F/_R pairs with common prefixes.
+  inputs:
+  - ERR042228_F.fq.gz
+  - ERR042228_R.fq.gz
+  - ERR636028_F.fq.gz
+  - ERR636028_R.fq.gz
+  paired:
+    ERR042228:
+      forward: ERR042228_F.fq.gz
+      reverse: ERR042228_R.fq.gz
+    ERR636028:
+      forward: ERR636028_F.fq.gz
+      reverse: ERR636028_R.fq.gz