Rare disease

The informatics of developmental phenotypes

Year: 2025 Venue: Kaufman’s Atlas of Mouse Development Supplement Authors: Paul N. Schofield, Robert Hoehndorf, Georgios V. Gkoutos, Cynthia L. Smith DOI: 10.1016/b978-0-443-23739-3.00012-2

Su1295: Chemically defined peptide-based matrices enabling the development of colorectal organoid models for therapeutic applications and disease modeling

Drug mechanisms Rare disease

Year: 2025 Venue: Gastroenterology Authors: Dana Alhattab, Duna Barakeh, Basma Khoja, Ahmad Elhadi, Jameel Miro, Saleh A. Alessy, Ahmed Alharbi, Manal Bokhary, May Alzahrani, Saga Ali, Wadha Almohamdi, Lama Hefni, Manola Moretti, Abeer Abdullah, Waleed Alomaim, Robert Hoehndorf, Charlotte Hauser, Saleh A. Alqahtani DOI: 10.1016/s0016-5085(25)02643-5

Sa1216: Development of colorectal cancer and matched healthy organoids from Saudi patients: a case study

Rare disease

Year: 2025 Venue: Gastroenterology Authors: Dana Alhattab, Duna Barakeh, Basma Khoja, Ahmad Elhadi, Jameel Miro, Saleh A. Alessy, Ahmed Alharbi, Manal Bokhary, May Alzahrani, Saga Ali, Wadha Almohamdi, Lama Hefni, Manola Moretti, Yang Liu, Marwa Abdelhakim, Abeer Abdullah, Waleed Alomaim, Robert Hoehndorf, Charlotte Hauser, Saleh A. Alqahtani DOI: 10.1016/s0016-5085(25)01866-9

An integrative, translational approach to understanding rare and orphan genetically based diseases

Ontology engineering Rare disease

Year: 2013 Venue: Interface Focus Authors: Robert Hoehndorf, Paul N. Schofield, Georgios V. Gkoutos DOI: 10.1098/rsfs.2012.0055 Abstract PhenomeNet is an approach for integrating phenotypes across species and identifying candidate genes for genetic diseases based on the similarity between a disease and animal model phenotypes. In contrast to 'guilt-by-association' approaches, PhenomeNet relies exclusively on the comparison of phenotypes to suggest candidate genes, and can, therefore, be applied to study the molecular basis of rare and orphan diseases for which the molecular basis is unknown

Mouse genetic and phenotypic resources for human genetics

Rare disease

Venue: Human Mutation Authors: Paul N. Schofield, Robert Hoehndorf, Georgios V. Gkoutos Abstract The use of model organisms to provide information on gene function has proved to be a powerful approach to our understanding of both human disease and fundamental mammalian biology. Large-scale community projects using mice, based on forward and reverse genetics, and now the pan-genomic phenotyping efforts of the International Mouse Phenotyping Consortium (IMPC), are generating resources on an unprecedented scale which will be extremely valuable to human genetics and medicine. We discuss the nature

New approaches to the representation and analysis of phenotype knowledge in human diseases and their animal models

Applied Ontology Rare disease

Venue: Briefings in Functional Genomics Authors: Paul N. Schofield, John P. Sundberg, Robert Hoehndorf, Georgios V. Gkoutos Abstract The systematic investigation of the phenotypes associated with genotypes in model organisms holds the promise of revealing genotype–phenotype relations directly and without additional, intermediate inferences. Large-scale projects are now underway to catalog the complete phenome of a species, notably the mouse. With the increasing amount of phenotype information becoming available, a major challenge that biology faces today is the systematic analysis of this

PhenomeNET: a whole-phenome approach to disease gene discovery

Rare disease Semantic similarity

Venue: Nucleic Acids Research Authors: Robert Hoehndorf, Paul N. Schofield, Georgios V. Gkoutos Abstract Phenotypes are investigated in model organisms to understand and reveal the molecular mechanisms underlying disease. Phenotype ontologies were developed to capture and compare phenotypes within the context of a single species. Recently, these ontologies were augmented with formal class definitions that may be utilized to integrate phenotypic data and enable the direct comparison of phenotypes between different species. We have developed a method to transform phenotype ontologies into a

EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay

Rare disease

Year: 2020 Venue: Clinical Genetics Authors: Muhammad Umair, Mariam Ballow, Abdulaziz Asiri, Yusra Alyafee, Abeer Tuwaijri, Kheloud M. Alhamoudi, Taghrid Aloraini, Marwa Abdelhakim, Azza Thamer Althagafi, Senay Kafkas, Lamia Alsubaie, Muhammad Talal Alrifai, Robert Hoehndorf, Ahmed Alfares, Majid Alfadhel DOI: 10.1111/cge.13842 Abstract In recent years, several genes have been implicated in the variable disease presentation of global developmental delay (GDD) and intellectual disability (ID). The endoplasmic reticulum membrane protein complex (EMC) family is known to be involved in GDD and ID

Causal relationships between diseases mined from the literature improve the use of polygenic risk scores

Rare disease

Year: 2024 Venue: Bioinformatics Authors: Sumyyah Toonsi, Iris Ivy Gauran, Hernando Ombao, Paul N Schofield, Robert Hoehndorf DOI: 10.1093/bioinformatics/btae639 Abstract The data are available through https://github.com/bio-ontology-research-group/causal-relations-between-diseases.

Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project

Rare disease

Year: 2024 Venue: Human Genomics Authors: Sarah L. Stenton, Melanie C. O’Leary, Gabrielle Lemire, Grace E. VanNoy, Stephanie DiTroia, Vijay S. Ganesh, Emily Groopman, Emily O’Heir, Brian Mangilog, Ikeoluwa Osei-Owusu, Lynn S. Pais, Jillian Serrano, Moriel Singer-Berk, Ben Weisburd, Michael W. Wilson, Christina Austin-Tse, Marwa Abdelhakim, Azza Althagafi, Giulia Babbi, Riccardo Bellazzi, Samuele Bovo, Maria Giulia Carta, Rita Casadio, Pieter-Jan Coenen, Federica De Paoli, Matteo Floris, Manavalan Gajapathy, Robert Hoehndorf, Julius O. B. Jacobsen, Thomas Joseph, Akash Kamandula, Panagiotis

Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

Neuro-Symbolic AI Rare disease

Year: 2018 Venue: Bioinformatics Authors: Mona Alshahrani, Robert Hoehndorf Abstract Motivation: In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease's (or patient's) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well

Towards similarity-based differential diagnostics for common diseases

Rare disease

Year: 2021 Venue: Computers in Biology and Medicine Authors: Luke T. Slater, Andreas Karwath, John A. Williams, Sophie Russell, Silver Makepeace, Alexander Carberry, Robert Hoehndorf, Georgios V. Gkoutos DOI: 10.1016/j.compbiomed.2021.104360 Abstract Ontology-based phenotype profiles have been utilised for the purpose of differential diagnosis of rare genetic diseases, and for decision support in specific disease domains. Particularly, semantic similarity facilitates diagnostic hypothesis generation through comparison with disease phenotype profiles. However, the approach has not been applied

Semantic prioritization of novel causative genomic variants

Rare disease Semantic similarity

Year: 2017 Venue: PLOS Computational Biology Authors: Imane Boudellioua, Rozaimi B. Mahamad Razali, Maxat Kulmanov, Yasmeen Hashish, Vladimir B. Bajic, Eva Goncalves-Serra, Nadia Schoenmakers, Georgios V. Gkoutos, Paul N. Schofield, Robert Hoehndorf DOI: 10.1371/journal.pcbi.1005500 Abstract Author summary We address the problem of how to distinguish which of the many thousands of DNA sequence variants carried by an individual with a rare disease is responsible for the disease phenotypes. This can help clinicians arrive at a diagnosis, but also can be instrumental in improving our

PathoPhenoDB: linking human pathogens to their disease phenotypes in support of infectious disease research

Rare disease

Year: 2019 Venue: Scientific Data Authors: Senay Kafkas, Marwa Abdelhakim, Yasmeen Hashish, Maxat Kulmanov, Marwa Abdellatif, Paul N Schofield, Robert Hoehndorf DOI: 10.1101/489971 Abstract Understanding the relationship between the pathophysiology of infectious disease, the biology of the causative agent and the development of therapeutic and diagnostic approaches is dependent on the synthesis of a wide range of types of information. Provision of a comprehensive and integrated disease phenotype knowledgebase has the potential to provide novel and orthogonal sources of information for the

Ontology based mining of pathogen--disease associations from literature

Applied Ontology Rare disease

Year: 2019 Venue: Journal of Biomedical Semantics Authors: Senay Kafkas, Robert Hoehndorf Acknowledged projects ccf-microbial-cell-factories crg-bio2vec

OligoPVP: Phenotype-driven analysis of individual genomic information to prioritize oligogenic disease variants

Rare disease

Year: 2018 Venue: Scientific Reports Authors: Imane Boudellioua, Maxat Kulmanov, Paul N Schofield, Georgios V Gkoutos, Robert Hoehndorf Abstract Purpose: An increasing number of Mendelian disorders have been identified for which two or more variants in one or more genes are required to cause the disease, or significantly modify its severity or phenotype. It is difficult to discover such interactions using existing approaches. The purpose of our work is to develop and evaluate a system that can identify combinations of variants underlying oligogenic diseases in individual whole exome or whole

Genomic landscape of retinoblastoma: Insights into risk stratification and precision pediatric Neuro-Oncology

Rare disease

Year: 2025 Venue: Neuro-Oncology Pediatrics Authors: Azza Maktabi, Yang Liu, Saleh Almesfer, Marwa Abdelhakim, Hind Aldakhil, Maxat Kulmanov, Deepak P Edward, Robert Hoehndorf, Malak Abedalthagafi DOI: 10.1093/neuped/wuaf017 Abstract Abstract Background Retinoblastoma is the most common intraocular malignancy of childhood, yet its genomic landscape remains incompletely defined, particularly in understudied populations. Beyond RB1 loss, the contribution of additional somatic and germline alterations to disease heterogeneity and clinical behavior is unclear. Methods We performed whole-exome

Nail abnormalities identified in an ageing study of 30 inbred mouse strains

Rare disease

Year: 2019 Venue: Experimental Dermatology Authors: Sarah C. Linn, Allison M. Mustonen, Kathleen A. Silva, Victoria E. Kennedy, Beth A. Sundberg, Lesley S. Bechtold, Sarah M. Alghamdi, Robert Hoehndorf, Paul N. Schofield, John P. Sundberg DOI: 10.1111/exd.13759 Abstract In a large-scale ageing study, 30 inbred mouse strains were systematically screened for histologic evidence of lesions in all organ systems. Ten strains were diagnosed with similar nail abnormalities. The highest frequency was noted in NON/ShiLtJ mice. Lesions identified fell into two main categories: acute to chronic

The application of Large Language Models to the phenotype-based prioritization of causative genes in rare disease patients

Rare disease

Year: 2025 Venue: Scientific Reports Authors: Senay Kafkas, Marwa Abdelhakim, Azza Althagafi, Sumyyah Toonsi, Malak Alghamdi, Paul N. Schofield, Robert Hoehndorf DOI: 10.1038/s41598-025-99539-y Abstract Computational methods for identifying gene-disease associations can use both genomic and phenotypic information to prioritize genes and variants that may be associated with genetic diseases. Phenotype-based methods commonly rely on comparing phenotypes observed in a patient with databases of genotype-to-phenotype associations using measures of semantic similarity. They are constrained by the

Starvar: symptom-based tool for automatic ranking of variants using evidence from literature and genomes

Rare disease

Year: 2023 Venue: BMC Bioinformatics Authors: Senay Kafkas, Marwa Abdelhakim, Mahmut Uludag, Azza Althagafi, Malak Alghamdi, Robert Hoehndorf DOI: 10.1186/s12859-023-05406-w Abstract Abstract Background Identifying variants associated with diseases is a challenging task in medical genetics research. Current studies that prioritize variants within individual genomes generally rely on known variants, evidence from literature and genomes, and patient symptoms and clinical signs. The functionalities of the existing tools, which rank variants based on given patient symptoms and clinical signs, are

Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

Rare disease Semantic similarity

Year: 2015 Venue: Scientific Reports Authors: Robert Hoehndorf, Paul N Schofield, Georgios V Gkoutos Abstract Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic

Genomic landscape in Saudi patients with hepatocellular carcinoma using whole-genome sequencing: a pilot study

Rare disease

Year: 2023 Venue: Frontiers in Gastroenterology Authors: Mazen Hassanain, Yang Liu, Weam Hussain, Albandri Binowayn, Duna Barakeh, Ebtehal Alsolme, Faisal AlSaif, Ghaida Almasaad, Mohammed AlSwayyed, Maram Alaqel, Rana Aljunidel, Sherin Abdelrahman, Charlotte A. E. Hauser, Saleh Alqahtani, Robert Hoehndorf, Malak Abedalthagafi DOI: 10.3389/fgstr.2023.1205415 Abstract Our findings indicate that most of the HCC patients possess cancer-related genetic variants, and the altered pathways in these patients exhibit similarities. Notably, resistant patients exhibit a higher frequency of aberrations in

DeepPVP: phenotype-based prioritization of causative variants using deep learning

Neuro-Symbolic AI Rare disease

Year: 2019 Venue: BMC Bioinformatics Authors: Imane Boudellioua, Maxat Kulmanov, Paul N Schofield, Georgios V Gkoutos, Robert Hoehndorf Abstract Background: Prioritization of variants in personal genomic data is a major challenge. Recently, computational methods that rely on comparing phenotype similarity have shown to be useful to identify causative variants. In these methods, pathogenicity prediction is combined with a semantic similarity measure to prioritize not only variants that are likely to be dysfunctional but those that are likely involved in the pathogenesis of a patient{

Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics

Rare disease

Year: 2015 Venue: Nature Genetics Authors: Martin Hrab\ve de Angelis, George Nicholson, Mohammed Selloum, Jacqueline K White, Hugh Morgan, Ramiro Ramirez-Solis, Tania Sorg, Sara Wells, Helmut Fuchs, Martin Fray, David J Adams, Niels C Adams, Thure Adler, Antonio Aguilar-Pimentel, Dalila Ali-Hadji, Gregory Amann, Philippe Andr\'e, Sarah Atkins, Aurelie Auburtin, Abdel Ayadi, Julien Becker, Lore Becker, Elodie Bedu, Raffi Bekeredjian, Marie-Christine Birling, Andrew Blake, Joanna Bottomley, Michael R Bowl, V\'eronique Brault, Dirk H Busch, James N Bussell, Julia Calzada-Wack, Heather Cater

Ontology based text mining of gene-phenotype associations: application to candidate gene prediction

Rare disease

Year: 2019 Venue: Database Authors: Senay Kafkas, Robert Hoehndorf Abstract Gene–phenotype associations play an important role in understanding the disease mechanisms which is a requirement for treatment development. A portion of gene–phenotype associations are observed mainly experimentally and made publicly available through several standard resources such as MGI. However, there is still a vast amount of gene–phenotype associations buried in the biomedical literature. Given the large amount of literature data, we need automated text mining tools to alleviate the burden in manual curation of

Hyaline Arteriolosclerosis in 30 Strains of Aged Inbred Mice

Rare disease

Year: 2019 Venue: Veterinary Pathology Authors: Timothy K. Cooper, Kathleen A. Silva, Victoria E. Kennedy, Sarah M. Alghamdi, Robert Hoehndorf, Beth A. Sundberg, Paul N. Schofield, John P. Sundberg DOI: 10.1177/0300985819844822 Abstract During a screen for vascular phenotypes in aged laboratory mice, a unique discrete phenotype of hyaline arteriolosclerosis of the intertubular arteries and arterioles of the testes was identified in several inbred strains. Lesions were limited to the testes and did not occur as part of any renal, systemic, or pulmonary arteriopathy or vasculitis phenotype

Predicting candidate genes from phenotypes, functions and anatomical site of expression

Rare disease

Year: 2021 Venue: Bioinformatics Authors: Jun Chen, Azza Althagafi, Robert Hoehndorf DOI: 10.1093/bioinformatics/btaa879 Abstract Supplementary data are available at Bioinformatics online.

CAGI6 ID panel challenge: assessment of phenotype and variant predictions in 415 children with neurodevelopmental disorders (NDDs)

Rare disease

Year: 2025 Venue: Human Genetics Authors: Maria Cristina Aspromonte, Alessio Del Conte, Shaowen Zhu, Wuwei Tan, Yang Shen, Yexian Zhang, Qi Li, Maggie Haitian Wang, Giulia Babbi, Samuele Bovo, Pier Luigi Martelli, Rita Casadio, Azza Althagafi, Sumyyah Toonsi, Maxat Kulmanov, Robert Hoehndorf, Panagiotis Katsonis, Amanda Williams, Olivier Lichtarge, Su Xian, Wesley Surento, Vikas Pejaver, Sean D. Mooney, Uma Sunderam, Rajgopal Srinivasan, Alessandra Murgia, Damiano Piovesan, Silvio C. E. Tosatto, Emanuela Leonardi DOI: 10.1007/s00439-024-02722-w Abstract Abstract The Genetics of

Ontology-based prediction of cancer driver genes

Applied Ontology Rare disease

Year: 2019 Venue: Scientific Reports Authors: Sara Althubaiti, Andreas Karwath, Ashraf Dallol, Adeeb Noor, Shadi Salem Alkhayyat, Rolina Alwassia, Katsuhiko Mineta, Takashi Gojobori, Andrew D Beggs, Paul N Schofield, Georgios V Gkoutos, Robert Hoehndorf Abstract Identifying and distinguishing cancer driver genes among thousands of candidate mutations remains a major challenge. Accurate identification of driver genes and driver mutations is critical for advancing cancer research and personalizing treatment based on accurate stratification of patients. Due to inter-tumor genetic heterogeneity

DeepSVP: integration of genotype and phenotype for structural variant prioritization using deep learning

Rare disease

Year: 2022 Venue: Bioinformatics Authors: Azza Althagafi, Lamia Alsubaie, Nagarajan Kathiresan, Katsuhiko Mineta, Taghrid Aloraini, Fuad Al Mutairi, Majid Alfadhel, Takashi Gojobori, Ahmad Alfares, Robert Hoehndorf DOI: 10.1093/bioinformatics/btab859 Abstract Supplementary data are available at Bioinformatics online.

Contribution of model organism phenotypes to the computational identification of human disease genes

Rare disease Semantic similarity

Year: 2022 Venue: Disease Models & Mechanisms Authors: Sarah Alghamdi, Paul N. Schofield, Robert Hoehndorf DOI: 10.1242/dmm.049441 Abstract Computing phenotypic similarity helps identify new disease genes and diagnose rare diseases. Genotype-phenotype data from orthologous genes in model organisms can compensate for lack of human data and increase genome coverage. In the past decade, cross-species phenotype comparisons have proven valuble, and several ontologies have been developed for this purpose. The relative contribution of different model organisms to computational identification of

What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations

Rare disease

Year: 2020 Venue: BMC Medical Genomics Authors: Ahmed Alfares, Lamia Alsubaie, Taghrid Aloraini, Aljoharah Alaskar, Azza Althagafi, Ahmed Alahmad, Mamoon Rashid, Abdulrahman Alswaid, Ali Alothaim, Wafaa Eyaid, Faroug Ababneh, Mohammed Albalwi, Raniah Alotaibi, Mashael Almutairi, Nouf Altharawi, Alhanouf Alsamer, Marwa Abdelhakim, Senay Kafkas, Katsuhiko Mineta, Nicole Cheung, Abdallah M. Abdallah, Stine B\"uchmann-M\oller, Yoshinori Fukasawa, Xiang Zhao, Issaac Rajan, Robert Hoehndorf, Fuad Al Mutairi, Takashi Gojobori, Majid Alfadhel DOI: 10.1186/s12920-020-00743-8 Abstract There was no

DeepPheno: Predicting single gene loss-of-function phenotypes using an ontology-aware hierarchical classifier

Neuro-Symbolic AI Rare disease

Year: 2020 Venue: PLOS Computational Biology Authors: Maxat Kulmanov, Robert Hoehndorf DOI: 10.1371/journal.pcbi.1008453 Abstract Author summary Gene–phenotype associations can help to understand the underlying mechanisms of many genetic diseases. However, experimental identification, often involving animal models, is time consuming and expensive. Computational methods that predict gene–phenotype associations can be used instead. We developed DeepPheno, a novel approach for predicting the phenotypes resulting from a loss of function of a single gene. We use gene functions and gene expression

Rare disease

The diagnosis of rare and Mendelian disease has been transformed by exome and genome sequencing, but interpretation remains the bottleneck: a typical patient genome contains tens of thousands of rare variants, only one or a few of which are causative. Effective diagnostic support requires the integration of patient-specific molecular data with structured background knowledge about genes, phenotypes, and disease mechanisms. We develop methods, anchored on the PhenomeNET phenotype network and the PVP family of variant prioritisation tools, that combine automated reasoning over phenotype

DeepViral

Rare disease Phenotype informatics genomics

Predicts virus–host protein-protein interactions from sequence and infectious-disease phenotypes; trained jointly across coronaviruses, influenza, and other RNA viruses. Get it GitHub: https://github.com/bio-ontology-research-group/DeepViral ★ 12 Developed in projects CompleX: Variant Prioritization in Complex Disease Category: Variant and Disease Prioritization

predCAN

Rare disease Phenotype informatics genomics

Ontology-based prediction of cancer driver genes by integrating phenotype, pathway and function knowledge with somatic-variant features. Get it GitHub: https://github.com/bio-ontology-research-group/predCAN ★ 5 Developed in projects CompleX: Variant Prioritization in Complex Disease Category: Variant and Disease Prioritization

GenomeLinter

Rare disease Phenotype informatics genomics

AI-powered clinical decision-support tool that ingests annotated VCFs and synthesises diagnostic interpretations for rare-disease patients without requiring deep bioinformatics expertise. Get it GitHub: https://github.com/bio-ontology-research-group/genome-linter Category: Variant and Disease Prioritization

INDIGENA

Rare disease Phenotype informatics genomics

Inductive prediction of disease–gene associations from phenotype ontologies; generalises to unseen diseases via ontology-aware embeddings. Get it GitHub: https://github.com/bio-ontology-research-group/indigena ★ 1 Developed in projects CompleX: Variant Prioritization in Complex Disease Category: Variant and Disease Prioritization

STARVar

Rare disease Phenotype informatics genomics

Symptom-based tool for automatic ranking of variants using evidence from the biomedical literature and population genomes; combines text mining with phenotype matching. Get it GitHub: https://github.com/bio-ontology-research-group/STARVar ★ 7 Developed in projects CompleX: Variant Prioritization in Complex Disease Category: Variant and Disease Prioritization

EmbedPVP

Rare disease Phenotype informatics genomics

Embedding-based phenotype-aware variant predictor that ranks candidate causative variants using joint sequence- and phenotype-derived representations. Get it GitHub: https://github.com/bio-ontology-research-group/EmbedPVP ★ 8 Developed in projects CompleX: Variant Prioritization in Complex Disease Category: Variant and Disease Prioritization

DeepSVP

Rare disease Phenotype informatics genomics

Prioritizes structural and copy-number variants by combining patient phenotype with gene-function similarity learned from biomedical ontologies. Get it GitHub: https://github.com/bio-ontology-research-group/DeepSVP ★ 18 Developed in projects CompleX: Variant Prioritization in Complex Disease A public Saudi pangenome as reference for genomics in the Middle East Category: Variant and Disease Prioritization

PhenomeNET-VP

Rare disease Phenotype informatics genomics

Phenotype-driven variant prioritization for whole-exome and whole-genome sequencing data; widely used implementation of the phenotype-aware variant ranking approach. Get it GitHub: https://github.com/bio-ontology-research-group/phenomenet-vp ★ 43 Developed in projects CompleX: Variant Prioritization in Complex Disease Category: Variant and Disease Prioritization

Safana Bakheet

Rare disease Ontology engineering Neuro-Symbolic AI Biomedical Informatics

Safana Bakheet completed her MSc in Bioengineering at KAUST in 2025 under the supervision of Robert Hoehndorf. Her work was carried out in collaboration with Fernando Zhapa-Camacho and developed methods for prioritising disease-causing genes by combining ontology-based phenotype representations with supervised knowledge graph embeddings. Her thesis, An Inductive, Supervised Gene-Disease Associations Method, introduces a ranking model that scores candidate disease-causing genes based on the similarity of their associated phenotypes, represented in the Mammalian Phenotype Ontology (MP) and the

Amal Alhelal

protein function Rare disease bioengineering Biomedical Informatics

Amal Alhelal completed her MSc in Bioengineering at KAUST in 2024 under the supervision of Robert Hoehndorf. She was a student in the Bioinformatics and Machine Learning track of the Bioengineering programme, based at the Computational Bioscience Research Center (CBRC), and defended her thesis in May 2024. Her thesis, titled Protein functional domain identification methodology (defended under the working title Exploring the association between protein functional domains and pathogenicity information derived from AI tools), investigated computational approaches to delineate functional domains

Improvement of genetic variant prioritization technology

Mon, May 18 2026

Applied Ontology Neuro-Symbolic AI Rare disease

By 2018 the PhenomeNET Variant Predictor (PVP) had been validated as a research tool for prioritizing causative variants in Mendelian disease, and a clear question had emerged: could the same phenotype-driven, knowledge-graph-based machinery be retargeted to cancer, where the variant landscape is somatic, heterogeneous, and dominated by combinations of driver and passenger mutations rather than single pathogenic alleles? This one-year KAUST Center Partnership Fund project (2018–2019, OSR-2018-CPF-3657-0; with Schofield in Cambridge, Gkoutos in Birmingham, and Bajic at KAUST) was the

Whole genome sequencing of rare disease patients

Mon, May 18 2026

Rare disease

This 2019 Office of Sponsored Research pilot was a short, focused collaboration with KAUST Health to put whole-genome sequencing in front of rare-disease cases for the first time at KAUST. Saudi Arabia has an unusually high prevalence of recessive Mendelian disease driven by high rates of consanguinity, yet at the time first-tier genomic diagnosis was rarely available locally. The pilot was designed to test the end-to-end pathway — patient identification, sample handling, sequencing, variant calling, phenotype-driven prioritization, and clinical interpretation — inside KAUST rather than

Improving health of Saudi population

Mon, May 18 2026

Neuro-Symbolic AI Rare disease

Translating modern biomedical knowledge into healthcare for Saudi Arabia requires methods that work on local data: a population with high consanguinity, a distinctive spectrum of inborn errors of metabolism, and clinical phenotypes that are not always well represented in international reference resources. The project, led by Hoehndorf at KAUST's Computational Bioscience Research Center (CBRC, now dissolved), developed health-informatics methods and resources oriented towards Saudi-population data, with a focus on rare disease, drug treatment, and the formal representation of phenotype

CompleX: Variant Prioritization in Complex Disease

Mon, May 18 2026

Applied Ontology Neuro-Symbolic AI Rare disease Semantic similarity

The hardest cases in clinical genome sequencing are the ones where no single variant explains the disease. As Mendelian gene discovery slows and the diagnostic rate for whole-exome sequencing stalls below 50%, growing evidence points to oligogenic and polygenic origins: combinations of medium-rare or common alleles that, individually, look unremarkable. Population-level approaches lack the power to find them, and traditional single-gene Mendelian reasoning ignores them. The CompleX project (2019–2021, with the Universities of Cambridge and Birmingham) set out to break this impasse by extending

IBNSINA-QI: Integrating Biomedical Networks and Semantic Information for Neural network Analysis of Quantitative Information

Mon, May 18 2026

Applied Ontology Neuro-Symbolic AI Rare disease

Biological measurements are inherently high-dimensional and heterogeneous: omics platforms produce thousands to millions of features per individual, and they coexist with qualitative information such as diagnoses, phenotype calls, and prescriptions. Biomedical ontologies and knowledge graphs encode rich qualitative background knowledge, but they are largely disconnected from the quantitative measurements that gave rise to the categorical phenotypes in the first place. Conversely, graph neural networks and other methods that handle quantitative data on graphs do not yet exploit the formal

Disease Models from Patient-derived Leukemic Cells in Biomimetic Peptide Scaffolds for Precision Medicine Applications

Sun, May 17 2026

Neuro-Symbolic AI Rare disease

Acute myeloid leukemia (AML) has a five-year survival rate of roughly 24% in Saudi Arabia and is the second most common adult leukemia subtype in the Kingdom. Treatment selection still rests on cytogenetic risk stratification — a coarse instrument that misses much of the molecular heterogeneity now known to drive drug response. Compounding the problem, almost every published AML drug-response prediction model has been trained on Western cohorts, and existing 3D culture systems for leukemia rely on animal-derived matrices that resist standardisation. This project (2023–2026, KAUST Smart-Health

KAUST Center of Excellence for Generative AI (Health and Wellness, BCB theme)

Sun, May 17 2026

Drug mechanisms Neuro-Symbolic AI Rare disease

The KAUST Center of Excellence for Generative AI has a Health and Wellness theme, and within that theme the Bioinformatics and Computational Biology (BCB) workstream is responsible for the bio-side problems that generic generative models cannot solve on their own: protein and antibody design, population-specific drug development, and clinical foundation models that can actually reason with structured biomedical knowledge. The BORG group leads the neuro-symbolic and ontology-based components of this work (Sub-WBS FCC/1/5940-07-02), in partnership with Xin Gao's group on AI/drug design and the

Personalized cancer treatment prediction (KCSH Pathway to Impact 2025)

Sun, May 17 2026

Neuro-Symbolic AI Rare disease

Predicting which drug will work for which patient is one of the oldest unsolved problems in oncology, and it is especially acute in Saudi Arabia, where colorectal cancer is the most common cancer in men and is shifting toward younger ages, and hepatocellular carcinoma incidence has roughly doubled in two decades. Contemporary machine learning models for drug response largely ignore the decades of curated biological knowledge that surrounds them, and they are almost never trained on Saudi populations. This project, funded under the KCSH Pathway to Impact 2025 call and running 2025-2026, aims to

A public Saudi pangenome as reference for genomics in the Middle East

Sun, May 17 2026

genomics Neuro-Symbolic AI Rare disease

Human reference genomes such as GRCh38 are built largely from a single individual of mixed African-European ancestry, and they systematically misrepresent the genetic structure of populations that diverged from that backbone, especially populations like those of the Arabian Peninsula that were historically organised in tribal structures with high in-tribe marriage. The consequence in clinical practice is a reference bias that inflates the apparent variant count by millions, complicates interpretation, and lengthens diagnostic turnaround. With more than half of marriages in Saudi Arabia