Biology subjects

Baldwin, N.

Publications and source records attributed to Baldwin, N..

5 recordsLinked to original sources

bioRxiv2026

Preclinical Safety Evaluation of Human Lactoferrin Alpha (Effera(R))

The preclinical safety of human-equivalent lactoferrin alpha (heqLF; effera(R)), produced by Komagataella phaffii, was evaluated to support its use as a food ingredient in infant formula and products for young children. Genotoxicity was assessed using a bacterial reverse mutation (Ames) assay in five strains of Salmonella typhimurium and Escherichia coli, and an in vitro micronucleus assay in TK6 cells. Both studies followed OECD guidelines and were conducted up to the recommended limit concentrations (5000 {micro}g/plate and 2000 {micro}g/mL, respectively). A 14-day non-GLP juvenile dose range-finding study and a 13-week GLP juvenile rat toxicity study with a 4-week recovery phase were conducted under ICH S11 guidance. Neonatal Sprague-Dawley rats received heqLF at 0, 1500, 3000, or 5000 mg/kg body weight/day by twice-daily oral gavage from postnatal day 7 to 98. Bovine lactoferrin (bLF) and whey protein at 5000 mg/kg body weight/day served as reference controls. heqLF was non-mutagenic and non-clastogenic in both genotoxicity assays. In the 13-week juvenile rat study, no heqLF-related mortality, clinical signs, developmental, neurobehavioral, or immune toxicity effects were observed. Minor, non-adverse renal findings consistent with high protein intake were observed and largely reversed during recovery. Clinical pathology parameters fully resolved during recovery. Toxicokinetic evaluation showed no systemic accumulation. Based on the absence of toxicologically relevant adverse findings, heqLF is well tolerated at doses up to 5000 mg/kg body weight/day, establishing a no observed adverse effect level (NOAEL) of 5000 mg/kg/day, the highest dose tested, and supporting its safety across intended populations from birth to adulthood.

pharmacology and toxicology↗

bioRxiv2020

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

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 focused blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates. As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: therapeutic development relevance, SARS biology relevance and immunological relevance. Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients.

immunology↗

bioRxiv2019

A Transcriptome Fingerprinting Assay for Clinical Immune Monitoring

BackgroundWhile our understanding of the role that the immune system plays in health and disease is growing at a rapid pace, available clinical tools to capture this complexity are lagging. We previously described the construction of a third-generation modular transcriptional repertoire derived from genome-wide transcriptional profiling of blood of 985 subjects across 16 diverse immunologic conditions, which comprises 382 distinct modules.\n\nResultsHere we describe the use of this modular repertoire framework for the development of a targeted transcriptome fingerprinting assay (TFA). The first step consisted in down-selection of the number of modules to 32, on the basis of similarities in changes in transcript abundance and functional interpretation. Next down-selection took place at the level of each of the 32 modules, with each one of them being represented by four transcripts in the final 128 gene panel. The assay was implemented on both the Fluidigm high throughput microfluidics PCR platform and the Nanostring platform, with the list of assays target probes being provided for both. Finally, we provide evidence of the versatility of this assay to assess numerous immune functions in vivo by demonstrating applications in the context of disease activity assessment in systemic lupus erythematosus and longitudinal immune monitoring during pregnancy.\n\nConclusionsThis work demonstrates the utility of data-driven network analysis applied to large-scale transcriptional profiling to identify key markers of immune responses, which can be downscaled to a rapid, inexpensive, and highly versatile assay of global immune function applicable to diverse investigations of immunopathogenesis and biomarker discovery.

immunology↗

bioRxiv2019

A Novel Repertoire of Blood Transcriptome Modules Based on Co-expression Patterns Across Sixteen Disease and Physiological States

As the capacity for generating large scale 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. It is meant to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome profiling data. It is supported by customized resources, which include analysis workflows, fingerprint grid plots data visualizations, interactive web applications providing access to a vast number of module-specific functional profiling reports, reference transcriptional profiles and give users the ability to visualize of changes in transcript abundance across the modular repertoire at different granularity levels. A use case focusing on a set of six modules comprising interferon-inducible genes is also provided. Altogether we hope that this resource will also serve as a framework for improving over time our collective understanding of the immunobiology underlying blood transcriptome profiling data.

immunology↗

bioRxiv2017

A systems approach to the characterization and classification of T-cell responses

Types of T-cell responses are categorized on the basis of a limited number of molecular markers selected using a priori knowledge about T-cell immunobiology. We sought to develop a novel systems-based approach for the creation of an unbiased framework enabling assessment of antigenic-peptide specific T-cell responses in vitro. A meta-analysis of transcriptome data from PBMCs stimulated with a wide range of peptides identified patterns of gene regulation that provided an unbiased classification of types of antigen-specific responses. Further analysis yielded new insight about the molecular processes engaged following antigenic stimulation. This led for instance to the identification of transcription factors not previously studied in the context of T-cell differentiation. Taken together this profiling approach can serve as a basis for the unbiased characterization of antigen-specific responses and as a foundation for the development of novel systems-based immune profiling assays.

genomics↗