Digital Commons Network^™

Automating Candidate Gene Prioritization With Large Language Models: From Naive Scoring To Literature-Grounded Validation., Taushif Khan, Mohammed Toufiq, Marina Yurieva, Nitaya Indrawattana, Akanitt Jittmittraphap, Nathamon Kosoltanapiwat, Pornpan Pumirat, Passanesh Sukphopetch, Muthita Vanaporn, Karolina Palucka, Basirudeen Syed Ahamed Kabeer, Darawan Rinchai, Damien Chaussabel

Faculty Research 2025

MOTIVATION: Identifying promising therapeutic targets from thousands of genes in transcriptomic studies remains a major bottleneck in biomedical research. While large language models (LLMs) show potential for gene prioritization, they suffer from hallucination and lack systematic validation against expert knowledge.

RESULTS: The framework identified 609 sepsis-relevant genes with >94% filtering efficiency, demonstrating strong enrichment for inflammatory pathways including TNF-α signaling, complement activation, and interferon responses. Literature validation yielded 30 ultra-high confidence therapeutic candidates, including both established sepsis genes (IL10, TREM1, S100A9, NLRP3) and novel targets warranting investigation. Benchmark validation against expert-curated databases achieved 71.2% recall, with systematic correlation between computational …

The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons Of The Transcriptomic Landscapes Across Mouse Models, Ling Cai, Fangjiang Wu, Qinbo Zhou, Ying Gao, Bo Yao, Ralph J Deberardinis, George K Acquaah-Mensah, Vassilis Aidinis, Jennifer E Beane, Shyam Biswal, Ting Chen, Carla P Concepcion-Crisol, Barbara M Grüner, Deshui Jia, Robert A Jones, Jonathan M Kurie, Min Gyu Lee, Per Lindahl, Yonathan Lissanu, Corina Lorz, David Macpherson, Rosanna Martinelli, Pawel K Mazur, Sarah A Mazzilli, Shinji Mii, Herwig P Moll, Roger A Moorehead, Edward E Morrisey, Sheng Rong Ng, Matthew G Oser, Arun R Pandiri, Charles A Powell, Giorgio Ramadori, Mirentxu Santos, Eric L Snyder, Rocio Sotillo, Kang-Yi Su, Tetsuro Taki, Kekoa Taparra, Phuoc T Tran, Yifeng Xia, J Edward Van Veen, Monte M Winslow, Guanghua Xiao, Charles M Rudin, Trudy G Oliver, Yang Xie, John D Minna

Faculty, Staff and Student Publications

Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, …

Gene Promoters Are Genomically Encoded To Facilitate Histone Exchange/Incorporation, Blaine Bartholomew

Faculty, Staff and Student Publications

Gene promoters are intrinsically hardwired not only to facilitate transcription preinitiation complex formation but also the release of paused RNA polymerase by H2A.Z. A new PLOS Biology study reveals poly (dA) tracts at promoters positively stimulate H2A.Z incorporation by the SWR complex in yeast.

Fusionpub, A Therapeutic Landscape Of Human Fusion Genes, Himansu Kumar, Abayomi Adegunlehin, Zikang Chen, Pora Kim

Faculty, Staff and Student Publications

To advance the development of fusion protein-targeting therapeutics, it is crucial to understand how patients with fusion oncoproteins have been treated and what small molecules have been studied. To fill this gap, we developed FusionPub, a knowledgebase of the therapeutic landscape of human fusion genes. We searched PubMed abstracts for 107K human fusion genes with 14K drugs. We also searched PubMed abstracts for 18K human fusion proteins, considering all gene synonyms of individual partner genes with 14K drugs. After manual curation, we found 17 342 records from 9623 PubMed abstracts. For these fusion genes and drugs, we provide a summary …

Updates To The Alliance Of Genome Resources Central Infrastructure., The Alliance Of Genome Resources Consortium

Faculty Research 2024

The Alliance of Genome Resources (Alliance) is an extensible coalition of knowledgebases focused on the genetics and genomics of intensively studied model organisms. The Alliance is organized as individual knowledge centers with strong connections to their research communities and a centralized software infrastructure, discussed here. Model organisms currently represented in the Alliance are budding yeast, Caenorhabditis elegans, Drosophila, zebrafish, frog, laboratory mouse, laboratory rat, and the Gene Ontology Consortium. The project is in a rapid development phase to harmonize knowledge, store it, analyze it, and present it to the community through a web portal, direct downloads, and application programming interfaces …

Single-Cell Dna Methylome And 3d Multi-Omic Atlas Of The Adult Mouse Brain, Hanqing Liu, Qiurui Zeng, Jingtian Zhou, Anna Bartlett, Bang-An Wang, Peter Berube, Wei Tian, Mia Kenworthy, Jordan Altshul, Joseph R Nery, Huaming Chen, Rosa G Castanon, Songpeng Zu, Yang Eric Li, Jacinta Lucero, Julia K Osteen, Antonio Pinto-Duarte, Jasper Lee, Jon Rink, Silvia Cho, Nora Emerson, Michael Nunn, Carolyn O'Connor, Zhanghao Wu, Ion Stoica, Zizhen Yao, Kimberly A Smith, Bosiljka Tasic, Chongyuan Luo, Jesse R Dixon, Hongkui Zeng, Bing Ren, M Margarita Behrens, Joseph R Ecker

Faculty, Staff and Student Publications

Cytosine DNA methylation is essential in brain development and is implicated in various neurological disorders. Understanding DNA methylation diversity across the entire brain in a spatial context is fundamental for a complete molecular atlas of brain cell types and their gene regulatory landscapes. Here we used single-nucleus methylome sequencing (snmC-seq3) and multi-omic sequencing (snm3C-seq)1 technologies to generate 301,626 methylomes and 176,003 chromatin conformation–methylome joint profiles from 117 dissected regions throughout the adult mouse brain. Using iterative clustering and integrating with companion whole-brain transcriptome and chromatin accessibility datasets, we constructed a methylation-based cell taxonomy with 4,673 cell groups and 274 …

Evolutionary Action-Machine Learning Model Identifies Candidate Genes Associated With Early-Onset Coronary Artery Disease, Dillon Shapiro, Kwanghyuk Lee, Jennifer Asmussen, Thomas Bourquard, Olivier Lichtarge

Faculty, Staff and Students Publications

Background Coronary artery disease is a primary cause of death around the world, with both genetic and environmental risk factors. Although genome-wide association studies have linked >100 unique loci to its genetic basis, these only explain a fraction of disease heritability. Methods and Results To find additional gene drivers of coronary artery disease, we applied machine learning to quantitative evolutionary information on the impact of coding variants in whole exomes from the Myocardial Infarction Genetics Consortium. Using ensemble-based supervised learning, the Evolutionary Action-Machine Learning framework ranked each gene's ability to classify case and control samples and identified 79 significant associations. …

Structural Variants Drive Context-Dependent Oncogene Activation In Cancer, Zhichao Xu, Dong-Sung Lee, Sahaana Chandran, Victoria T Le, Rosalind Bump, Jean Yasis, Sofia Dallarda, Samantha Marcotte, Benjamin Clock, Nicholas Haghani, Chae Yun Cho, Kadir C Akdemir, Selene Tyndale, P Andrew Futreal, Graham Mcvicker, Geoffrey M Wahl, Jesse R Dixon

Faculty, Staff and Student Publications

Higher-order chromatin structure is important for the regulation of genes by distal regulatory sequences. Structural variants (SVs) that alter three-dimensional (3D) genome organization can lead to enhancer-promoter rewiring and human disease, particularly in the context of cancer3. However, only a small minority of SVs are associated with altered gene expression4,5, and it remains unclear why certain SVs lead to changes in distal gene expression and others do not. To address these questions, we used a combination of genomic profiling and genome engineering to identify sites of recurrent changes in 3D genome structure in cancer and determine the effects of specific …

Rapid Induction Of The Unfolded Protein Response And Apoptosis By Estrogen Mimic Ttc-352 For The Treatment Of Endocrine-Resistant Breast Cancer, Balkees Abderrahman, Philipp Y Maximov, Ramona F Curpan, Sean W Fanning, Jay S Hanspal, Ping Fan, Charles E Foulds, Yue Chen, Anna Malovannaya, Antrix Jain, Rui Xiong, Geoffrey L Greene, Debra A Tonetti, Gregory R J Thatcher, V Craig Jordan

Faculty, Staff and Students Publications

Patients with long-term estrogen-deprived breast cancer (BC), after resistance to tamoxifen or aromatase inhibitors develops, can experience tumor regression when treated with estrogens. Estrogen’s anti-tumor effect is attributed to apoptosis via the estrogen receptor (ER). Estrogen treatment can have unpleasant gynecological and non-gynecological adverse events thus the development of safer estrogenic agents remains a clinical priority. Here, we study synthetic selective estrogen mimics (SEMs) BMI-135 and TTC-352, and the naturally-occurring estrogen estetrol (E4), which are proposed as safer estrogenic agents compared to 17β-estradiol (E2), for the treatment of endocrine-resistant BC. TTC-352 and E4 are being evaluated in BC clinical trials. …

Statistical Methods For Assessing Structural Change In Human & Microbial Genomes, Xuan Zhu

Dissertations and Theses (Open Access)

Genetic sequencing has been recognized as an effective approach to accurately address biological problems, such as clinical detection of disease, mutation discovery, and targeting specific biomarkers associated with complex diseases. Compared with conventional Sanger sequencing, next-generation sequencing costs much less due to massively parallel high-throughput sequencing. However, due to large numbers of short read sequences, the accuracy of high-throughput sequencing data remains a challenge in that the data obtained from next-generation sequencing often has higher error rates, which may impact downstream genomic analysis. Even if the downstream genomic analysis performs well, the quality of the result will still be impacted …

Bcl-2 Promoter Sequence G-Quadruplex Interactions With Three Planar And Non-Planar Cationic Porphyrins: Tmpyp4, Tmpyp3, And Tmpyp2., Vu H. Le, Narayana Nagesh, Edwin A. Lewis

CAS Publications

The interactions of three related cationic porphyrins, TMPyP4, TMPyP3 and TMPyP2, with a WT 39-mer Bcl-2 promoter sequence G-quadruplex were studied using Circular Dichroism, ESI mass spectrometry, Isothermal Titration Calorimetry, and Fluorescence spectroscopy. The planar cationic porphyrin TMPyP4 (5, 10, 15, 20-meso-tetra (N-methyl-4-pyridyl) porphine) is shown to bind to a WT Bcl-2 G-quadruplex via two different binding modes, an end binding mode and a weaker mode attributed to intercalation. The related non-planar ligands, TMPyP3 and TMPyP2, are shown to bind to the Bcl-2 G-quadruplex by a single mode. ESI mass spectrometry experiments confirmed that the saturation stoichiometry is 4:1 for …

Brovine: Mammary Gland Gene Database, Therin C. Irwin

Computer Science and Software Engineering

Brovine is used by the Animal Science department at Cal Poly to catalog and analyze genetic information. Brovine, or the Mammary Gland Gene Database, is a system used to store and categorize genetic information which is gathered through experimentation and through TESS, a web application that lets users search through catalogs of similar genetic information. This document describes the purpose, use, and maintenance of Brovine.

The Complex Transcriptional Landscape Of The Anucleate Human Platelet., Paul F. Bray, Steven E. Mckenzie, Leonard Edelstein, Srikanth Nagalla, Kathleen Delgrosso, Adam Ertel, Joan Kupper, Yi Jing, Eric R. Londin, Phillipe Loher, Huang-Wen Chen, Paolo Fortina, Isidore Rigoutsos

Cardeza Foundation for Hematologic Research

BACKGROUND: Human blood platelets are essential to maintaining normal hemostasis, and platelet dysfunction often causes bleeding or thrombosis. Estimates of genome-wide platelet RNA expression using microarrays have provided insights to the platelet transcriptome but were limited by the number of known transcripts. The goal of this effort was to deep-sequence RNA from leukocyte-depleted platelets to capture the complex profile of all expressed transcripts.

RESULTS: From each of four healthy individuals we generated long RNA (≥40 nucleotides) profiles from total and ribosomal-RNA depleted RNA preparations, as well as short RNA (<40 >nucleotides) profiles. Analysis of ~1 billion reads revealed that coding …

Arabidopsis Bhlh100 And Bhlh101 Control Iron Homeostasis Via A Fit-Independent Pathway, Alicia B. Sivitz, Victor Hermand, Catherine Curie, Grégory Vert

Dartmouth Scholarship

Iron deficiency induces a complex set of responses in plants, including developmental and physiological changes, to increase iron uptake from soil. In Arabidopsis, many transporters involved in the absorption and distribution of iron have been identified over the past decade. However, little is known about the signaling pathways and networks driving the various responses to low iron. Only the basic helix–loop–helix (bHLH) transcription factor FIT has been shown to control the expression of the root iron uptake machinery genes FRO2 and IRT1. Here, we characterize the biological role of two other iron-regulated transcription factors, bHLH100 and bHLH101, in iron homeostasis. …

The Ethics Of Genetic Patenting And The Subsequent Implications On The Future Of Health Care, Suzanne Ratcliffe

Touro Law Review

No abstract provided.

Systems Approach Identifies An Organic Nitrogen-Responsive Gene Network That Is Regulated By The Master Clock Control Gene Cca1, Rodrigo A. Gutierrez, Trevor L. Stokes, Karen Thum, Xiaodong Xu, Mariana Obertello, Manpreet S. Katari, Milos Tanurdzic, Alexis Dean, Damion C. Nero, C Robertson Mcclung, Gloria M. Coruzzi

Dartmouth Scholarship

Understanding how nutrients affect gene expression will help us to understand the mechanisms controlling plant growth and development as a function of nutrient availability. Nitrate has been shown to serve as a signal for the control of gene expression in Arabidopsis. There is also evidence, on a gene-by-gene basis, that downstream products of nitrogen (N) assimilation such as glutamate (Glu) or glutamine (Gln) might serve as signals of organic N status that in turn regulate gene expression. To identify genome-wide responses to such organic N signals, Arabidopsis seedlings were transiently treated with ammonium nitrate in the presence or absence of …

Transcriptional Regulatory Network Analysis During Epithelial-Mesenchymal Transformation Of Retinal Pigment Epithelium., Craig H Pratt, Rajanikanth Vadigepalli, Praveen Chakravarthula, Gregory E Gonye, Nancy J Philp, Gerald B Grunwald

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

PURPOSE: Phenotypic transformation of retinal pigment epithelial (RPE) cells contributes to the onset and progression of ocular proliferative disorders such as proliferative vitreoretinopathy (PVR). The formation of epiretinal membranes in PVR may involve an epithelial-mesenchymal transformation (EMT) of RPE cells as part of an aberrant wound healing response. While the underlying mechanism remains unclear, this likely involves changes in RPE cell gene expression under the control of specific transcription factors (TFs). Thus, the purpose of the present study was to identify TFs that may play a role in this process.

METHODS: Regulatory regions of genes that are differentially regulated during …

Fully Codon-Optimized Luciferase Uncovers Novel Temperature Characteristics Of The Neurospora Clock, Van D. Gooch, Arun Mehra, Luis F. Larrondo, Julie Fox, Melissa Touroutoutoudis, Jennifer J. Loros, Jay C. Dunlap

Dartmouth Scholarship

We report the complete reconstruction of the firefly luciferase gene, fully codon optimized for expression in Neurospora crassa. This reporter enhances light output by approximately 4 log orders over that with previously available versions, now producing light that is visible to the naked eye and sufficient for monitoring the activities of many poorly expressed genes. Time lapse photography of strains growing in race tubes, in which the frq or eas/ccg-2 promoter is used to drive luciferase, shows the highest levels of luciferase activity near the growth front and newly formed conidial bands. Further, we have established a sorbose medium colony …

Integration Without Unification: An Argument For Pluralism In The Biological Sciences, Sandra D. Mitchell, Michael R. Dietrich

Dartmouth Scholarship

In this article, we consider the tension between unification and pluralism in biological theory. We begin with a consideration of historical efforts to establish a unified understanding of evolution in the neo‐Darwinian synthesis. The fragmentation of the evolutionary synthesis by molecular evolution suggests the limitations of the general unificationist ideal for biology but not necessarily for integrating explanations. In the second half of this article, we defend a specific variety of pluralism that allows for the integration required for explanations of complex phenomena without unification on a large scale.

Phylogeographic Analyses Of Obligate And Facultative Cave Crayfish Species On The Cumberland Plateau Of The Southern Appalachians, Jennifer Elizabeth Buhay

Theses and Dissertations

Cave systems and their unique biota are widely viewed as highly endangered, yet very little is known about basic life history, ecology, distributions, habitat requirements, and evolutionary relationships of subterranean species. The crux of the problem in cave studies is the assumption that traditionally defined morpho-species represent distinct evolutionary lineages. Convergence is exhibited in the morphologies of many animal groups, vertebrate and invertebrate, which leads to confusion in diagnosing species' boundaries, geographic distributions, gene flow routes, and imperilment. This dissertation research includes phylogeographic analyses of freshwater cave-dwelling crayfishes in the Southern Appalachians, a global hotspot of subterranean biodiversity. By examining …

Proteolytic Release Of Cd44 Intracellular Domain And Its Role In The Cd44 Signaling Pathway., I Okamoto, Y Kawano, D Murakami, T Sasayama, N Araki, T Miki, A J Wong, H Saya

Department of Microbiology and Immunology Faculty Papers

CD44 is a widely distributed cell surface adhesion molecule and is implicated in diverse biological processes. However, the nature of intracellular signaling triggered by CD44 remains to be elucidated. Here, we show that CD44 undergoes sequential proteolytic cleavage in the ectodomain and intracellular domain, resulting in the release of a CD44 intracellular domain (ICD) fragment. Consequently, CD44ICD acts as a signal transduction molecule, where it translocates to the nucleus and activates transcription mediated through the 12-O-tetradecanoylphorbol 13-acetate-responsive element, which is found in numerous genes involved in diverse cellular processes. Expression of an uncleavable CD44 mutant as well as metalloprotease inhibitor …

The Logical Next Step? An International Perspective On The Issues Of Human Cloning And Genetic Technology, Jason T. Corsover

ILSA Journal of International & Comparative Law

"If you're a scientist, you believe that it is good to find out how the world works; that it is good to find what the realities are; that it is good to turn over to mankind at large the greatest possible power to control the world…”

- Robert Oppenheimer on the Manhattan Project