diff --git a/gnu/packages/bioinformatics.scm b/gnu/packages/bioinformatics.scm
index 93458fb1621..4f4be10a472 100644
--- a/gnu/packages/bioinformatics.scm
+++ b/gnu/packages/bioinformatics.scm
@@ -3613,63 +3613,64 @@ phylogenetic markers, and can also scale to very large phylogenies comprising
 (define-public python-pybedtools
   (package
     (name "python-pybedtools")
-    (version "0.10.0")
-    (source (origin
-              (method url-fetch)
-              (uri (pypi-uri "pybedtools" version))
-              (sha256
-               (base32
-                "0q8if5bd8zgv5xvr5zs4pj8y60yzl8i5jz8xfk6bw4xh4fnvlvqs"))))
+    (version "0.12.0")
+    (source
+     (origin
+       (method url-fetch)
+       (uri (pypi-uri "pybedtools" version))
+       (sha256
+        (base32 "0jbjaj0n34k64jp5q3l653qrrxwd8d276hqbq1ii7j3rcngyr1l7"))
+       (snippet
+        ;; Force the Cythonization of C++ files to guard against compilation
+        ;; problems.
+        #~(begin
+            (use-modules (guix build utils))
+            (use-modules (srfi srfi-26))
+            (let ((cython-sources (map (cut string-drop-right <> 4)
+                                       (find-files "." "\\.pyx$")))
+                  (c/c++-files (find-files "." "\\.(c|cpp|cxx)$")))
+              (define (strip-extension filename)
+                (string-take filename (string-index-right filename #\.)))
+              (define (cythonized? c/c++-file)
+                (member (strip-extension c/c++-file) cython-sources))
+              (for-each delete-file (filter cythonized? c/c++-files)))))))
     (build-system pyproject-build-system)
     (arguments
      (list
-      #:modules '((srfi srfi-26)
-                  (guix build utils)
-                  (guix build python-build-system)
-                  (guix build pyproject-build-system))
+      #:build-backend "setuptools.build_meta"
+      ;; tests: 508 passed, 1 deselected, 3 xfailed
       #:test-flags
-      ;; Requires internet access.
-      '(list "-k" "not test_chromsizes")
+      #~(list "--pyargs" "pybedtools"
+              ;; ValueError: It appears you don't have an internet connection
+              ;; -- unable to get chromsizes from UCSC
+              "--deselect=test/test_helpers.py::test_chromsizes")
       #:phases
-      '(modify-phases %standard-phases
-         (add-after 'unpack 'fix-references
-           (lambda _
-             (substitute* "pybedtools/test/test_issues.py"
-               (("'/bin/bash'") (string-append "'" (which "bash") "'")))))
-         ;; Force the Cythonization of C++ files to guard against compilation
-         ;; problems.
-         (add-after 'unpack 'remove-cython-generated-files
-           (lambda _
-             (let ((cython-sources (map (cut string-drop-right <> 4)
-                                        (find-files "." "\\.pyx$")))
-                   (c/c++-files (find-files "." "\\.(c|cpp|cxx)$")))
-               (define (strip-extension filename)
-                 (string-take filename (string-index-right filename #\.)))
-               (define (cythonized? c/c++-file)
-                 (member (strip-extension c/c++-file) cython-sources))
-               (for-each delete-file (filter cythonized? c/c++-files)))))
-         (add-after 'remove-cython-generated-files 'generate-cython-extensions
-           (lambda _
-             (invoke "python" "setup.py" "cythonize")))
-         (add-before 'check 'build-extensions
-           (lambda _
-             ;; Cython extensions have to be built before running the tests.
-             (invoke "python" "setup.py" "build_ext" "--inplace"))))))
+      #~(modify-phases %standard-phases
+          (add-after 'unpack 'fix-references
+            (lambda _
+              (substitute* "pybedtools/test/test_issues.py"
+                (("'/bin/bash'") (string-append "'" (which "bash") "'")))))
+          (add-before 'build 'generate-cython-extensions
+            (lambda _
+              (invoke "python" "setup.py" "cythonize")))
+          (add-before 'check 'remove-local-source
+            (lambda _
+              (delete-file-recursively "pybedtools"))))))
     (propagated-inputs
-     (list bedtools samtools
+     (list bedtools
            kentutils ;for bedGraphToBigWig
            python-numpy
            python-pandas
            python-psutil
            python-pysam
-           python-pyyaml))
+           python-pyyaml
+           samtools))
     (inputs
      (list zlib))
     (native-inputs
      (list python-cython
            python-pytest
-           python-setuptools
-           python-wheel))
+           python-setuptools))
     (home-page "https://pythonhosted.org/pybedtools/")
     (synopsis "Python wrapper for BEDtools programs")
     (description