A training curriculum for retrieving, structuring, and aggregating information derived from the biomedical literature and large-scale data repositories

Background: Biomedical research over the past two decades has become data and information rich. This trend has been in large part driven by the development of systems-scale molecular profiling capabilities and by the increasingly large volume of publications contributed by the biomedical research community. It has therefore become important for early career researchers to learn to leverage this wealth of information in their own research. Methods: Here we describe in detail a training curriculum focusing on the development of foundational skills necessary to retrieve, structure, and aggregate information available from vast stores of publicly available information. It is provided along with supporting material and an illustrative use case. The stepwise workflow encompasses; 1) Selecting a candidate gene; 2) Retrieving background information about the gene; 3) Profiling its literature; 4) Identifying in the literature instances where its transcript abundance changes in blood of patients; 5) Retrieving transcriptional profiling data from public blood transcriptome and reference datasets; and 6) Drafting a manuscript, submitting it for peer-review, and publication. Results: This resource may be leveraged by instructors who wish to organize hands-on workshops. It can also be used by independent trainees as a self-study toolkit. The workflow presented as proof-of- concept was designed to establish a resource for assessing a candidate gene’s potential utility as a blood transcriptional biomarker. Trainees will learn to retrieve literature and public transcriptional profiling data associated with a specific gene of interest. They will also learn to extract, structure, and aggregate this information to support downstream interpretation efforts as well as the preparation of a manuscript. Conclusions: This resource should support early career researchers in their efforts to acquire skills that will permit them to leverage the vast amounts of publicly available large-scale profiling data

Baseline immune states (BIS) associated with vaccine responsiveness and factors that shape the BIS.

Vaccines are among the greatest inventions in medicine, leading to the elimination or control of numerous diseases, including smallpox, polio, measles, rubella, and, most recently, COVID-19. Yet, the effectiveness of vaccines varies among individuals. In fact, while some recipients mount a robust response to vaccination that protects them from the disease, others fail to respond. Multiple clinical and epidemiological factors contribute to this heterogeneity in responsiveness. Systems immunology studies fueled by advances in single-cell biology have been instrumental in uncovering pre-vaccination immune cell types and genomic features (i.e., the baseline immune state, BIS) that have been associated with vaccine responsiveness. Here, we review clinical factors that shape the BIS, and the characteristics of the BIS associated with responsiveness to frequently studied vaccines (i.e., influenza, COVID-19, bacterial pneumonia, malaria). Finally, we discuss potential strategies to enhance vaccine responsiveness in high-risk groups, focusing specifically on older adults

Blood gene transcript signature profiling in pregnancies resulting in preterm birth: a systematic review

To pursue a systematic review and summarise the current evidence for the potential of transcriptome molecular profiling in investigating the preterm phenotype.; We systematically reviewed the literature, using readily available electronic databases (i.e. PubMed/Medline, Embase, Scopus and Web of Science) from inception until March 2020 to identify investigations of maternal blood-derived RNA profiling in preterm birth (PTB). Studies were included if circulating coding or non-coding RNA was analysed in maternal blood during pregnancy and/or at delivery. Interventional trials were not included. The primary outcome was the availability of whole genome expression patterns evaluated in pregnancies resulting in preterm deliveries.; A total of 35 articles were included in the final analysis. Most of the studies were conducted in high-income countries and published in the last decade. Apart from spontaneous PTB, a variety of phenotypes leading to preterm delivery were reported. Differences in sampling methods, target gene selection and laboratory protocols severely limited any quantitative comparisons. Most of the studies revealed that gene expression profiling during pregnancy has high potential for identifying women at risk of spontaneous and/or non-spontaneous PTB as early as in the first trimester.; Assessing maternal blood-derived transcriptional signatures for PTB risk in pregnant women holds promise as a screening approach. However, longitudinally followed, prospective pregnancy cohorts are lacking. These are relevant for identifying causes leading to PTB and whether prediction of spontaneous PTB or co-morbidities associated with PTB is achievable. More emphasis on widely employed standardised protocols is required to ensure comparability of results

Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis

A diagnostic signature for sepsis caused by Burkholderia pseudomallei infection was identified from transcriptional profiling of the blood of septicemia patients

An interferon signature is associated with HAM/TSP but not viral containment in HTLV-1 infection

International audiencen.

Ribosomal protein mRNAs are translationally-regulated during human dendritic cells activation by LPS

International audienceBACKGROUND: Dendritic cells (DCs) are the sentinels of the mammalian immune system, characterized by a complex maturation process driven by pathogen detection. Although multiple studies have described the analysis of activated DCs by transcriptional profiling, recent findings indicate that mRNAs are also regulated at the translational level. A systematic analysis of the mRNAs being translationally regulated at various stages of DC activation was performed using translational profiling, which combines sucrose gradient fractionation of polysomal-bound mRNAs with DNA microarray analysis. RESULTS: Total and polysomal-bound mRNA populations purified from immature, 4 h and 16 h LPS-stimulated human monocyte-derived DCs were analyzed on Affymetrix microarrays U133 2.0. A group of 375 transcripts was identified as translationally regulated during DC-activation. In addition to several biochemical pathways related to immunity, the most statistically relevant biological function identified among the translationally regulated mRNAs was protein biosynthesis itself. We singled-out a cluster of 11 large ribosome proteins mRNAs, which are disengaged from polysomes at late time of maturation, suggesting the existence of a negative feedback loop regulating translation in DCs and linking ribosomal proteins to immuno-modulatory function. CONCLUSION: Our observations highlight the importance of translation regulation during the immune response, and may favor the identification of novel protein networks relevant for immunity. Our study also provides information on the potential absence of correlation between gene expression and protein production for specific mRNA molecules present in DCs

Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy

Rationale: Globally there are approximately 9 million new active tuberculosis cases and 1.4 million deaths annually . Effective antituberculosis treatment monitoring is difficult as there are no existing biomarkers of poor adherence or inadequate treatment earlier than 2 months after treatment initiation. Inadequate treatment leads to worsening disease, disease transmission and drug resistance. Objectives To determine if blood transcriptional signatures change in response to antituberculosis treatment and could act as early biomarkers of a successful response. METHODS: Blood transcriptional profiles of untreated active tuberculosis patients in South Africa were analysed before, during (2 weeks and 2 months), at the end of (6 months) and after (12 months) antituberculosis treatment, and compared to individuals with latent tuberculosis. An active-tuberculosis transcriptional signature and a specific treatment-response transcriptional signature were derived. The specific treatment response transcriptional signature was tested in two independent cohorts. Two quantitative scoring algorithms were applied to measure the changes in the transcriptional response. The most significantly represented pathways were determined using Ingenuity Pathway Analysis. RESULTS: An active tuberculosis 664-transcript signature and a treatment specific 320-transcript signature significantly diminished after 2 weeks of treatment in all cohorts, and continued to diminish until 6 months. The transcriptional response to treatment could be individually measured in each patient. CONCLUSIONS: Significant changes in the transcriptional signatures measured by blood tests were readily detectable just 2 weeks after treatment initiation. These findings suggest that blood transcriptional signatures could be used as early surrogate biomarkers of successful treatment response

Author Correction: Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza.

In the version of this article initially published, a source of funding was not included in the Acknowledgements section. That section should include the following: P.J.M.O. was supported by EU FP7 PREPARE project 602525. The error has been corrected in the HTML and PDF version of the article