From gene modules to gene markers: an integrated AI-human approach selects CD38 to represent plasma cell-associated transcriptional signatures.

Background: Knowledge-driven prioritization of candidate genes derived from large-scale molecular profiling data for targeted transcriptional profiling assays is challenging due to the vast amount of biomedical literature that needs to be harnessed. We present a workflow leveraging Large Language Models (LLMs) to prioritize candidate genes within module M12.15, a plasma cell-associated module from the BloodGen3 repertoire, by integrating knowledge-driven prioritization with data-driven analysis of transcriptome profiles.

Whole-Blood Longitudinal Molecular Profiling Maps the Road of Graft Versus Host Disease (GVHD).

Graft versus host disease (GVHD) and the graft versus tumor (GVT) effect after allogeneic hematopoietic cell transplantation (allo-HCT) result from complex interactions between the donor immune system and the recipient environment. High-temporal longitudinal monitoring might be necessary to identify triggering events of GVHD and GVT and to intercept these events before their occurrence. But it would require an overall considerable amount of blood by venipuncture, which is unfeasible in such a fragile population.

The integrative genomic and functional immunological analyses of colorectal cancer initiating cells to modulate stemness properties and the susceptibility to immune responses.

Background: Colorectal cancer (CRC) initiating cells (CICs) possess self-renewal capabilities and are pivotal in tumor recurrence and resistance to conventional therapies, including immunotherapy. The mechanisms underlying their interaction with immune cells remain unclear.

Methods: We conducted a multi-omics analysis-encompassing DNA methylation, total RNA sequencing, and microRNAs (miRNAs; N = 800) profiling on primary CICs and differentiated tumor cell lines, including autologous pairs.

The molecular landscape of sepsis severity in infants: enhanced coagulation, innate immunity, and T cell repression.

Introduction: Sepsis remains a major cause of mortality and morbidity in infants. In recent years, several gene marker strategies for the early identification of sepsis have been proposed but only a few have been independently validated for adult cohorts and applicability to infant sepsis remains unclear. Biomarkers to assess disease severity and risks of shock also represent an important unmet need.

A data browsing application for accessing gene and module-level blood transcriptome profiles of healthy pregnant women from high- and low-resource settings.

Transcriptome profiling data, generated via RNA sequencing, are commonly deposited in public repositories. However, these data may not be easily accessible or usable by many researchers. To enhance data reuse, we present well-annotated, partially analyzed data via a user-friendly web application.

Design of a targeted blood transcriptional panel for monitoring immunological changes accompanying pregnancy.

Background: Immunomodulatory processes exert steering functions throughout pregnancy. Detecting diversions from this physiologic immune clock may help identify pregnant women at risk for pregnancy-associated complications. We present results from a data-driven selection process to develop a targeted panel of mRNAs that may prove effective in detecting pregnancies diverting from the norm.

Harnessing large language models (LLMs) for candidate gene prioritization and selection.

Background: Feature selection is a critical step for translating advances afforded by systems-scale molecular profiling into actionable clinical insights. While data-driven methods are commonly utilized for selecting candidate genes, knowledge-driven methods must contend with the challenge of efficiently sifting through extensive volumes of biomedical information. This work aimed to assess the utility of large language models (LLMs) for knowledge-driven gene prioritization and selection.

A TRANSCRIPTOMIC APPRECIATION OF CHILDHOOD MENINGOCOCCAL AND POLYMICROBIAL SEPSIS FROM A PRO-INFLAMMATORY AND TRAJECTORIAL PERSPECTIVE, A ROLE FOR VASCULAR ENDOTHELIAL GROWTH FACTOR A AND B MODULATION?

This study investigated the temporal dynamics of childhood sepsis by analyzing gene expression changes associated with proinflammatory processes. Five datasets, including four meningococcal sepsis shock (MSS) datasets (two temporal and two longitudinal) and one polymicrobial sepsis dataset, were selected to track temporal changes in gene expression. Hierarchical clustering revealed three temporal phases: early, intermediate, and late, providing a framework for understanding sepsis progression.

Abundance of transcript is elevated during septic conditions: Perspectives obtained from a hands-on reductionist investigation.

Sepsis is a complex heterogeneous condition, and the current lack of effective risk and outcome predictors hinders the improvement of its management. Using a reductionist approach leveraging publicly available transcriptomic data, we describe a knowledge gap for the role of ACVR1B (activin A receptor type 1B) in sepsis. ACVR1B, a member of the transforming growth factor-beta (TGF-beta) superfamily, was selected based on the following: 1) induction upon exposure of neutrophils from healthy subjects with the serum of septic patients (GSE49755), and 2) absence or minimal overlap between ACVR1B, sepsis, inflammation, or neutrophil in published literature.

Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi-Bickel Syndrome.

Fanconi−Bickel Syndrome (FBS) is a rare disorder of carbohydrate metabolism that is characterized by the accumulation of glycogen mainly in the liver. It is inherited in an autosomal recessive manner due to mutations in the SLC2A2 gene. SLC2A2 encodes for the glucose transporter GLUT2 and is expressed in tissues that are involved in glucose homeostasis.

Transcriptomic profile investigations highlight a putative role for NUDT16 in sepsis.

Sepsis is an aberrant systemic inflammatory response mediated by the acute activation of the innate immune system. Neutrophils are important contributors to the innate immune response that controls the infection, but harbour the risk of collateral tissue damage such as thrombosis and organ dysfunction. A better understanding of the modulations of cellular processes in neutrophils and other blood cells during sepsis is needed and can be initiated via transcriptomic profile investigations.

SysInflam HuDB, a Web Resource for Mining Human Blood Cells Transcriptomic Data Associated with Systemic Inflammatory Responses to Sepsis.

Sepsis develops after a dysregulated host inflammatory response to a systemic infection. Identification of sepsis biomarkers has been challenging because of the multifactorial causes of disease susceptibility and progression. Public transcriptomic data are a valuable resource for mechanistic discoveries and cross-studies concordance of heterogeneous diseases.

Transcriptome and Literature Mining Highlight the Differential Expression of ERLIN1 in Immune Cells during Sepsis.

Sepsis results from the dysregulation of the host immune system. This highly variable disease affects 19 million people globally, and accounts for 5 million deaths annually. In transcriptomic datasets curated from public repositories, we observed a consistent upregulation (3.

Development of a fixed module repertoire for the analysis and interpretation of blood transcriptome data.

As the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles.

Immunomodulatory Effects of Vitamin D Supplementation in a Deficient Population.

In addition to its canonical functions, vitamin D has been proposed to be an important mediator of the immune system. Despite ample sunshine, vitamin D deficiency is prevalent (>80%) in the Middle East, resulting in a high rate of supplementation. However, the underlying molecular mechanisms of the specific regimen prescribed and the potential factors affecting an individual's response to vitamin D supplementation are not well characterized.

BloodGen3Module: blood transcriptional module repertoire analysis and visualization using R.

Motivation: We previously described the construction and characterization of fixed reusable blood transcriptional module repertoires. More recently we released a third iteration ('BloodGen3' module repertoire) that comprises 382 functionally annotated modules and encompasses 14 168 transcripts. Custom bioinformatic tools are needed to support downstream analysis, visualization and interpretation relying on such fixed module repertoires.

A Neutrophil-Driven Inflammatory Signature Characterizes the Blood Transcriptome Fingerprint of Psoriasis.

Transcriptome profiling approaches have been widely used to investigate the mechanisms underlying psoriasis pathogenesis. Most researchers have measured changes in transcript abundance in skin biopsies; relatively few have examined transcriptome changes in the blood. Although less relevant to the study of psoriasis pathogenesis, blood transcriptome profiles can be readily compared across various diseases.

A modular framework for the development of targeted Covid-19 blood transcript profiling panels.

Background: Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of targeted blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection.

Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data.

According to publicly available transcriptome datasets, the abundance of Annexin A3 (ANXA3) is robustly increased during the course of sepsis; however, no studies have examined the biological significance or clinical relevance of ANXA3 in this pathology. Here we explored this interpretation gap and identified possible directions for future research. Based on reference transcriptome datasets, we found that ANXA3 expression is restricted to neutrophils, is upregulated in vitro after exposure to plasma obtained from septic patients, and is associated with adverse clinical outcomes.

Influence of storage conditions of small volumes of blood on immune transcriptomic profiles.

Objective: Transcriptome analysis of human whole blood is used to discover biomarkers of diseases and to assess phenotypic traits. Here we have collected small volumes of blood in Tempus solution and tested whether different storage conditions have an impact on transcriptomic profiling. Fifty µl of blood were collected in 100µl of Tempus solutions, freezed at - 20 °C for 1 day and eventually thawed, stored and processed under five different conditions: (i) - 20 °C for 1 week; (ii) +4 °C for 1 week; (iii) room temperature for 1 week; (iv) room temperature for 1 day, - 20 °C for 1 day, room temperature until testing at day 7, (v) - 20 °C for 1 week, RNA was isolated and stored in GenTegra solution.

Long-Chain Acyl-CoA Synthetase 1 Role in Sepsis and Immunity: Perspectives From a Parallel Review of Public Transcriptome Datasets and of the Literature.

A potential role for the long-chain acyl-CoA synthetase family member 1 (ACSL1) in the immunobiology of sepsis was explored during a hands-on training workshop. Participants first assessed the robustness of the potential gap in biomedical knowledge identified via an initial screen of public transcriptome data and of the literature associated with ACSL1. Increase in ACSL1 transcript abundance during sepsis was confirmed in several independent datasets.