Evidence map›Paper›PMID 40055237›Full record

ArticleHuman genetics2025

Evaluation of enzyme activity predictions for variants of unknown significance in Arylsulfatase A.

Shantanu Jain, Marena Trinidad, Thanh Binh Nguyen, Kaiya Jones, Santiago Diaz Neto, Fang Ge, Ailin Glagovsky, Cameron Jones, Giankaleb Moran, Boqi Wang and 59 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

69 authors.

Shantanu JainThe Institute for Experiential AI, Northeastern University, Boston, MA, USA.
Marena TrinidadInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Thanh Binh NguyenSchool of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.
Kaiya JonesTuskegee University, Tuskegee, AL, USA.
Santiago Diaz NetoUniversidad Nacional de Rosario, Rosario, Argentina.
Fang GeState Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing, China.
Ailin GlagovskyNational University of Tucuman, Tucuman, Argentina.
Cameron JonesTuskegee University, Tuskegee, AL, USA.
Giankaleb MoranUniversity of Puerto Rico, San Juan, PR, USA.
Boqi WangDepartment of Bioinformatics and System Biology, University of California, San Diego, La Jolla, CA, USA.
Kobra RahimiDepartment of Computational Biology, School of Life Sciences, Ochanomizu University, Tokyo, Japan.
Sümeyra Zeynep ÇalıcıDepartment of Genomics, Faculty of Aquatic Science, Istanbul University, Istanbul, Turkey.
Luis R CedilloUniversity of Texas at El Paso, El Paso, USA.
Silvia BerardelliDepartment of Electrical, Computer, and Biomedical Engineering, University of Pavia, Pavia, Italy.
Buse ÖzdenDepartment of Molecular Biology and Genetics, Faculty of Arts and Sciences, Istanbul Kültür University, Istanbul, Turkey.
Ken ChenUniversity of California, Berkeley, Berkeley, CA, USA.
Panagiotis KatsonisDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Amanda WilliamsDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Olivier LichtargeDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Sadhna RanaTCS Research, Mumbai, India.
Swatantra PradhanTCS Research, Mumbai, India.
Rajgopal SrinivasanTCS Research, Mumbai, India.
Rakshanda SajeedTCS Research, Mumbai, India.
Dinesh JoshiTCS Research, Mumbai, India.
Eshel FaraggiResearch and Information Systems LLC, Indianapolis, IN, USA.
Robert JerniganRoy J. Carver Department of Biochemistry, Iowa State University, Ames, IA, USA.
Andrzej KloczkowskiInstitute for Genomic Medicine, The Research Institute at Nationwide Children'S Hospital, Columbus, OH, USA.
Jierui XuUniversity of California, Berkeley, Berkeley, CA, USA.
Zigang SongPeking University, Beijing, China.
Selen ÖzkanVall d'Hebron Institute of Research (VHIR), Barcelona, Spain.
Natàlia PadillaVall d'Hebron Institute of Research (VHIR), Barcelona, Spain.
Xavier de la CruzVall d'Hebron Institute of Research (VHIR), Barcelona, Spain.
Rocio Acuna-HidalgoNostos Genomics GmbH, Berlin, Germany.
Andrea GrafmüllerNostos Genomics GmbH, Berlin, Germany.
Laura T Jiménez BarrónNostos Genomics GmbH, Berlin, Germany.
Matteo ManfrediBiocomputing Group, University of Bologna, Bologna, Italy.
Castrense SavojardoBiocomputing Group, University of Bologna, Bologna, Italy.
Giulia BabbiBiocomputing Group, University of Bologna, Bologna, Italy.
Pier Luigi MartelliBiocomputing Group, University of Bologna, Bologna, Italy.
Rita CasadioBiocomputing Group, University of Bologna, Bologna, Italy.
Yuanfei SunDepartment of Electrical & Computer Engineering, Texas a&M University, College Station, TX, USA.
Shaowen ZhuDepartment of Electrical & Computer Engineering, Texas a&M University, College Station, TX, USA.
Yang ShenDepartment of Electrical & Computer Engineering, Texas a&M University, College Station, TX, USA.
Fabrizio PucciComputational Biology and Bioinformatics, Université Libre de Bruxelles, Bruxelles, Belgium.
Marianne RoomanComputational Biology and Bioinformatics, Université Libre de Bruxelles, Bruxelles, Belgium.
Gabriel CiaComputational Biology and Bioinformatics, Université Libre de Bruxelles, Bruxelles, Belgium.
Daniele RaimondiESAT-STADIUS, Katholieke Universiteit Leuven, Leuven, Belgium.
Pauline HermansComputational Biology and Bioinformatics, Université Libre de Bruxelles, Bruxelles, Belgium.
Sofia KweeUniversity of California, Berkeley, Berkeley, CA, USA.
Ella ChenUniversity of California, Berkeley, Berkeley, CA, USA.
Courtney Astore, San Diego, CA, USA.
Akash KamandulaKhoury College of Computer Sciences, Northeastern University, Boston, MA, USA.
Vikas PejaverInstitute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Rashika RamolaKhoury College of Computer Sciences, Northeastern University, Boston, MA, USA.
Michelle VelyunskiyKhoury College of Computer Sciences, Northeastern University, Boston, MA, USA.
Daniel ZeibergKhoury College of Computer Sciences, Northeastern University, Boston, MA, USA.
Reet MishraDepartment of Bioengineering, University of California, Berkeley, CA, USA.
Teague Sterling, San Anselmo, CA, USA.
Jennifer L GoldsteinDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jose Lugo-MartinezRay and Stephanie Lane Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA.
Sufyan Kazi, Houston, TX, USA.
Sindy LiUniversity of California, Berkeley, Berkeley, CA, USA.
Kinsey LongUniversity of California, Berkeley, Berkeley, CA, USA.
Steven E BrennerUniversity of California, Berkeley, Berkeley, CA, USA.
Constantina BakolitsaUniversity of California, Berkeley, Berkeley, CA, USA.
Predrag RadivojacKhoury College of Computer Sciences, Northeastern University, Boston, MA, USA.
Dean SuhrMLD Foundation, West Linn, OR, USA.
Teryn SuhrMLD Foundation, West Linn, OR, USA.
Wyatt T ClarkHoosier Bulk Transport, Greens Fork, IN, USA. wyatt.travis.clark@gmail.com.

Funding

Cognitive Computing of Alzheimer's Disease Genes and RiskU01AG068214 · NIA · BAYLOR COLLEGE OF MEDICINE · PI LICHTARGE, OLIVIER · 2021 to 2025
$4.4M
Center for Critical Assessment of Genome InterpretationU24HG007346 · NHGRI · UNIVERSITY OF CALIFORNIA BERKELEY · PI BRENNER, STEVEN E, IOANNIDIS, NILAH MONNIER · 2020 to 2025
$3.8M
Supporting IGVF by modeling genetics, function, and phenotype with machine learningU01HG012022 · NHGRI · NORTHEASTERN UNIVERSITY · PI Predrag Radivojac · 2021 to 2026
$3.4M
Unraveling molecular and system-level mechanisms of human disease-associated protein mutationsR35GM124952 · NIGMS · TEXAS ENGINEERING EXPERIMENT STATION · PI Yang Shen · 2017 to 2026
$2.9M
Novel Use of Genome Information to Understand MutationsR01HG012117 · NHGRI · IOWA STATE UNIVERSITY · PI JERNIGAN, ROBERT L, KLOCZKOWSKI, ANDRZEJ · 2021 to 2025
$2.3M
National Institutes of Health, United States AG068214National Institutes of Health, United States R01HG012117National Institutes of Health, United States R35GM124952National Institutes of Health, United States U01HG012022National Institutes of Health, United States U24HG007346NHGRI NIH HHS R01 HG012117NHGRI NIH HHS U01 HG012022NHGRI NIH HHS U24 HG007346NIA NIH HHS U01 AG068214NIGMS NIH HHS R35 GM124952Spanish Minesterio de Ciencia e Innocavion PID2019-11217RB-I00
6 · The paper itself

Abstract

Continued advances in variant effect prediction are necessary to demonstrate the ability of machine learning methods to accurately determine the clinical impact of variants of unknown significance (VUS). Towards this goal, the ARSA Critical Assessment of Genome Interpretation (CAGI) challenge was designed to characterize progress by utilizing 219 experimentally assayed missense VUS in the Arylsulfatase A (ARSA) gene to assess the performance of community-submitted predictions of variant functional effects. The challenge involved 15 teams, and evaluated additional predictions from established and recently released models. Notably, a model developed by participants of a genetics and coding bootcamp, trained with standard machine-learning tools in Python, demonstrated superior performance among submissions. Furthermore, the study observed that state-of-the-art deep learning methods provided small but statistically significant improvement in predictive performance compared to less elaborate techniques. These findings underscore the utility of variant effect prediction, and the potential for models trained with modest resources to accurately classify VUS in genetic and clinical research.

Indexed as

Cerebroside-SulfataseGenetic VariationHumansMachine LearningMutation, MissenseCerebroside-Sulfatase

Identifiers

PMID40055237
PMCPMC12122056

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.