diff --git a/biology/py-pydeseq2/Makefile b/biology/py-pydeseq2/Makefile
index 51cad42004b1..ca4f97fa32e9 100644
--- a/biology/py-pydeseq2/Makefile
+++ b/biology/py-pydeseq2/Makefile
@@ -1,27 +1,29 @@
 PORTNAME=	pydeseq2
-DISTVERSION=	0.5.2
-PORTREVISION=	3
+DISTVERSION=	0.5.4
 CATEGORIES=	biology python
 MASTER_SITES=	PYPI
 PKGNAMEPREFIX=	${PYTHON_PKGNAMEPREFIX}
 
 MAINTAINER=	jwb@FreeBSD.org
 COMMENT=	Python implementation of the popular DESeq2 R package
 WWW=		https://github.com/owkin/PyDESeq2
 
 LICENSE=	MIT
 LICENSE_FILE=	${WRKSRC}/LICENSE
 
+BUILD_DEPENDS=	${PYTHON_PKGNAMEPREFIX}hatchling>0:devel/py-hatchling@${PY_FLAVOR}
 RUN_DEPENDS=	${PYTHON_PKGNAMEPREFIX}anndata>=0.8.0:devel/py-anndata@${PY_FLAVOR} \
 		${PYTHON_PKGNAMEPREFIX}formulaic>=1.0.2:math/py-formulaic@${PY_FLAVOR} \
 		${PYTHON_PKGNAMEPREFIX}formulaic_contrasts>=0.2.0:math/py-formulaic-contrasts@${PY_FLAVOR} \
 		${PYTHON_PKGNAMEPREFIX}matplotlib>=3.6.2:math/py-matplotlib@${PY_FLAVOR} \
-		${PYTHON_PKGNAMEPREFIX}numpy>=1.16:math/py-numpy@${PY_FLAVOR} \
+		${PYNUMPY} \
 		${PYTHON_PKGNAMEPREFIX}pandas>=1.4.0:math/py-pandas@${PY_FLAVOR} \
 		${PYTHON_PKGNAMEPREFIX}scikit-learn>=1.1.0:science/py-scikit-learn@${PY_FLAVOR} \
 		${PYTHON_PKGNAMEPREFIX}scipy>1.11.0:science/py-scipy@${PY_FLAVOR}
 
 USES=		python
-USE_PYTHON=	autoplist distutils
+USE_PYTHON=	autoplist pep517
+
+NO_ARCH=	yes
 
 .include <bsd.port.mk>
diff --git a/biology/py-pydeseq2/distinfo b/biology/py-pydeseq2/distinfo
index 4ecfeca8f0d3..2aede254e5ae 100644
--- a/biology/py-pydeseq2/distinfo
+++ b/biology/py-pydeseq2/distinfo
@@ -1,3 +1,3 @@
-TIMESTAMP = 1751029007
-SHA256 (pydeseq2-0.5.2.tar.gz) = 9a124793f3155e40863f63cb92d73f815d01c6e0b3cc0d8e8730141c134c16f4
-SIZE (pydeseq2-0.5.2.tar.gz) = 51377
+TIMESTAMP = 1787830075
+SHA256 (pydeseq2-0.5.4.tar.gz) = 49d6f47840b5444ea2b69be7857c6c4e58f369066a0fb24bc52f7d3a62bbd92c
+SIZE (pydeseq2-0.5.4.tar.gz) = 790481