Biology subjects

Daoud, A.

Publications and source records attributed to Daoud, A..

7 recordsLinked to original sources

bioRxiv2026

Deep-Plant: a supervised foundation model for plant regulatory genomics

Large-scale sequence-to-function deep learning models have demonstrated unparalleled ability to model biological sequences and have revolutionized the field of regulatory genomics. However, the majority of such efforts have centered on human and mammalian systems, leaving plant regulatory genomics comparatively underexplored. To address this gap, we introduce DO_SCPLOWEEPC_SCPLOW-PO_SCPLOWLANTC_SCPLOW, a supervised foundation model trained to predict chromatin state directly from genomic sequence. In contrast to large language models, which are trained in a selfsupervised manner using sequence alone, our model is trained to predict chromatin state across tissues and conditions. Training the model on a large collection of genome-wide experiments including DNA accessibility, transcription factor binding, and histone modifications, provides it with added biological context beyond the sequence itself. We demonstrate that the resulting model is an effective platform for developing accurate models of regulatory activity relevant to gene expression and active enhancers, exhibiting large improvements in speed, accuracy, and interpretability over the complementary approach of fine-tuning DNA language models. DO_SCPLOWEEPC_SCPLOW-PO_SCPLOWLANTC_SCPLOW models are available in Arabidopsis and rice, and work well as a building block for sequence modeling in related species such as corn. Together, these results establish supervised, chromatin-informed foundation models as a practical and effective paradigm for regulatory sequence modeling in plants.

genomics↗

bioRxiv2025

NEUROG3 Is Sufficient to Drive Neuroendocrine Differentiation in Prostate Cancer Cells.

Treatment-emergent neuroendocrine prostate cancer (t-NEPC) arises following androgen deprivation therapy, leading to androgen-independent growth. Although multiple factors have been shown to be necessary for neuroendocrine differentiation (NED), their sufficiency has not been demonstrated. The prostate and colorectum share a common hindgut origin, and prostate neuroendocrine cell markers overlap with colorectal enteroendocrine cell (EEC) markers. Analysis of patient datasets revealed NEUROG3 amplification in both castration-resistant and neuroendocrine prostate cancers, correlating with poor survival. Because Neurogenin-3 (NEUROG3) is necessary and sufficient for EEC differentiation in the colorectum, we hypothesized that it could similarly drive NED in prostate cancer cells. A transient pulse of NEUROG3 repressed luminal identity and activated neuroendocrine programs, producing neuroendocrine cells within seven days. In summary, our findings identify NEUROG3 as a potential mediator of prostate cancer progression and establish a rapid in vitro model in which its transient activation is sufficient to initiate neuroendocrine differentiation.

cancer biology↗

bioRxiv2025

A technique for evaluating calcium flux in primary airway tissue at single cell resolution

Calcium signaling is critical in a multitude of biological processes, reinforcing the need to develop methods to study calcium flux in primary tissue. The study of live calcium mobilization into the cytosol is commonly studied by intracellular calcium dyes. However, the study of calcium mobilization at a single-cell resolution in differentiated, primary human tissue remains challenging. Here we present methodology to study calcium flux at single cell resolution in situ on primary tissue seeded on trans wells. As well, we developed a machine learning software that simplifies and streamlines analysis. SUMMARYLive intracellular calcium dyes enable our group to study cell type specific responses as fluorescent readouts in real time. Utilizing microscopic techniques, we devised methods to study calcium flux in individual cells on complex, differentiated primary tissues seeded on trans well inserts.

cell biology↗

bioRxiv2024

Benchmarking organ-specific responses to therapies in tissues differentiated from Cystic Fibrosis patient derived iPSCs

Cystic Fibrosis (CF) is a life-shortening disease that is caused by mutations in the CFTR gene, a gene that is expressed in multiple organs. There are several primary tissue models of CF disease, including nasal epithelial cultures and rectal organoids, that are effective in reporting the potential efficacy of mutation-targeted therapies called CFTR modulators. However, there is the well-documented variation in tissue dependent, therapeutic response amongst CF patients, even those with the same CF-causing mutation. Hence, there is an interest in developing strategies for benchmarking therapeutic efficacy in different organs relative to isogenic controls. In this study, we evaluated the CFTR chloride channel response to the highly effective CFTR modulator: Trikafta, in CF patient specific, iPSC-derived colonic and airway cultures relative to mutation-corrected (non-CF) tissues from that same individual. We measured pharmacological rescue in both tissues, but interestingly, Trikafta treatment resulted in different levels of functional rescue in the two tissues relative to the relevant isogenic control. This proof-of-concept study lays the groundwork for future comparisons of patient-specific CF therapeutic responses in both pulmonary and extra-pulmonary systems.

pharmacology and toxicology↗

bioRxiv2024

Human Pluripotent Stem Cell Derived Organoids Reveal a Role for WNT Signaling in Dorsal-Ventral Patterning of the Hindgut

The cloaca is a transient structure that forms in the terminal hindgut giving rise to the rectum dorsally and the urogenital sinus ventrally. Similarly, human hindgut cultures derived from human pluripotent stem cells generate human colonic organoids (HCOs) which also contain co-developing urothelial tissue. In this study, our goal was to identify pathways involved in cloacal patterning and apply this to human hindgut cultures. RNA-seq data comparing dorsal versus ventral cloaca in e10.5 mice revealed that WNT signaling was elevated in the ventral versus dorsal cloaca. Inhibition of WNT signaling in hindgut cultures biased their differentiation towards a colorectal fate. WNT activation biased differentiation towards a urothelial fate, giving rise to human urothelial organoids (HUOs). HUOs contained cell types present in human urothelial tissue. Based on our results, we propose a mechanism whereby WNT signaling patterns the ventral cloaca, prior to cloacal septation, to give rise to the urogenital sinus.

developmental biology↗

bioRxiv2024

Using large scale transfer learning to highlight the role of chromatin state in intron retention

Complex deep learning models trained on very large datasets have become key enabling tools for current research in natural language processing and computer vision. By providing pre-trained models that can be fine-tuned for specific applications, they enable researchers to create accurate models with minimal effort and computational resources. Large scale genomics deep learning models come in two flavors: the first are large language models of DNA sequences trained in a self-supervised fashion, similar to the corresponding natural language models; the second are supervised learning models that leverage large scale genomics datasets from ENCODE and other sources. We argue that these models are the equivalent of foundation models in natural language processing in their utility, as they encode within them chromatin state in its different aspects, providing useful representations that allow quick deployment of accurate models of gene regulation. We demonstrate this premise by leveraging the recently created Sei model to develop simple, interpretable models of intron retention, and demonstrate their advantage over models based on the DNA langauage model DNABERT-2. Our work also demonstrates the impact of chromatin state on the regulation of intron retention. Using representations learned by Sei, our model is able to discover the involvement of transcription factors and chromatin marks in regulating intron retention, providing better accuracy than a recently published custom model developed for this purpose. AvailabilityThe source code for this work is available at https://github.com/Addaoud/IntronRetention.

bioinformatics↗

bioRxiv2020

A lesson from COVID-19 on inaccessibility of web-based information for disabled populations worldwide

Many government websites and mobile content are inaccessible for people with vision, hearing, and cognitive disabilities. The COVID-19 pandemic highlighted these disparities when health authority website information, critical in providing resources for curbing the spread of the virus, remained inaccessible for disabled populations. The Web Content Accessibility Guidelines provide comparatively universally accepted guidelines for website accessibility. We utilized these parameters to examine the number of countries with or without accessible health authority websites. The resulting data indicate a dearth of countries with websites accessible for persons with disabilities. Methods of information dissemination must take into consideration individuals with disabilities, particularly in times of global health crises.

scientific communication and education↗