Search bioRxiv⌕ Search

bioRxiv · 10.64898/2026.07.28.741304

FITdb, an Integrated Functional Immunogenomics and Transcriptomics Database

Abstract

Genetic screens in immune cells enable the systematic interrogation of gene function at scale, uncovering key regulators of cell functions such as tumor cell killing and persistence. However, existing datasets typically focus on specific biological questions, employ targeted gene panels, are generated under diverse experimental conditions, and are not readily accessible, which together limit their integration and future usability. To address this, we developed the Functional Immunogenomics and Transcriptomics Database (FITdb), a freely accessible resource that harmonizes functional genomics datasets for the study of immune cell biology. FITdb currently integrates 43 independent functional genetics screens, including 32 pooled and 11 single-cell screens, spanning 20, 696 mouse genes and 22, 293 human genes across 199 immune cell types and conditions. All datasets are uniformly re-analyzed to enable cross-study comparisons. FITdb provides intuitive, gene-centric visualizations, detailed exploration of individual screens, and access to sgRNA-level data. Additionally, built-in tools such as "Compare MyGeneSet" and "Compare MyScreen" identify statistically significant overlaps between user-defined gene lists and functional gene sets in FITdb, and enable direct comparison of user-generated screening data with existing datasets, respectively. Together, FITdb provides a comprehensive, user-friendly platform for accelerating the discovery of immune regulatory programs. The database is freely available at https://fitdb.lji.org. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/741304v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@114d978org.highwire.dtl.DTLVardef@1d15d04org.highwire.dtl.DTLVardef@31c2f4org.highwire.dtl.DTLVardef@f63dfe_HPS_FORMAT_FIGEXP M_FIG C_FIG

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Cen, X., Ma, Q., Kim, K., Gamas-Vis, S., Goldrath, A. W., Heeg, M., Reina-Campos, M.. 2026-08-01. FITdb, an Integrated Functional Immunogenomics and Transcriptomics Database. https://doi.org/10.64898/2026.07.28.741304

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

ACE-engineered human iPSC-derived neutrophils enhance host defense against multidrug-resistant bacterial infections

Severe neutropenia predisposes patients to life-threatening infections, while donor-dependent granulocyte transfusions are limited by availability and variable cell quality. Here, we engineered human induced pluripotent stem cells (iPSCs) to constitutively or inducibly express angiotensin-converting enzyme (ACE) and differentiated them into functional ACE-engineered neutrophils (ACE-iNeu). ACE expression enhanced granulocytic maturation, reactive oxygen species generation, inflammatory cytokine production, and antimicrobial signaling. ACE-iNeu exhibited enhanced bactericidal activity against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa. Following adoptive transfer into neutropenic mice, ACE-iNeu significantly reduced circulating and tissue bacterial burdens. Integrated metabolomic and transcriptomic analyses revealed ACE-associated alterations in adenine nucleotide abundance and developmental and inflammatory pathways. Together, these findings establish ACE engineering as a strategy to enhance the production and antimicrobial function of human iPSC-derived neutrophils and support further preclinical development of engineered granulocyte therapies for severe drug-resistant infections.

immunology↗

Tetravalent dengue mRNA vaccination orchestrates balanced four-serotype immunity with durable memory and protection in mice.

An effective dengue vaccine must establish durable immunity across four dengue virus (DENV) serotypes, evade antibody-dependent enhancement (ADE), and overcome immune imprinting from prior exposure. Here, we developed TetprM-E mRNA-LNP, a tetravalent vaccine comprising LNP-formulated nucleoside-modified mRNAs encoding DENV1-4 precursor membrane-envelope (prM-E) antigens, and evaluated its immunogenicity, durability, protection and breath across serotype-specific immune backgrounds. Three immunization strategies elicited neutralizing titers greater than 1:1500 against each serotype. Passive transfer of immune sera conferred 100% survival and reduced viremia after lethal DENV2 challenge in immunocompromised mice. Vaccination induced DENV envelope (env)-specific CD8+T cells and CD4-dependent germinal-center responses. DENV env-binding antibodies persisted for 34 weeks alongside DENV env-specific memory B cells. Vaccine-elicited sera showed no measurable in vitro ADE. Although monovalent priming initially biased antibody responses, TetprM-E mRNA-LNP vaccination broadened neutralization across DENV1-4 regardless of priming serotype. Together, TetprM-E mRNA-LNP elicits broad, durable, and protective immunity despite serologic constraints from pre-existing immunity.

immunology↗

The antagonism of sex chromosomes and sex hormones dictates outcomes in Th17 cell-mediated central nervous system autoimmunity.

Biological sex traits are shaped by the combined effects of both sex hormones and chromosomes. How these factors interact in sex-related autoimmune diseases, such as multiple sclerosis (MS), has been a subject of intense recent interest. Here, using the Four Core Genotype (FCG) mouse model, in which these two variables can be disentangled, we describe an antagonism between sex hormones and chromosomes that potently influences outcomes in T helper 17 (Th17)-driven progressive central nervous system (CNS) autoimmunity. Male gonadal hormones dampen disease severity, irrespective of sex chromosome complement, by promoting a Wnt/{beta}-catenin signaling program associated with a homeostatic, non-pathogenic Th17 phenotype. By contrast, XY chromosomal complement exacerbates Th17 pathogenicity in a recipient sex-dependent manner; we identify the X-linked molecule SUV39H1 as an inhibitor of inflammatory Th17 cell function. Unexpectedly, we found that hormonally and chromosomally female FCG Th17 cells induced far more severe disease than WT female counterparts despite being genetically identical, pointing to a parental imprinting effect in dictating Th17 cell pathogenicity. These latter investigations uncovered Runx2, a transcription factor previously linked to developmental programs, as a novel negative regulator of the pathogenicity of Th17 cells. Together, our findings establish biological sex as a multilayered regulator of Th17 pathogenicity, revealing distinct and sometimes opposing contributions of hormones, chromosomes, and parental inheritance.

immunology↗