Life Sciences Research Articles

DECOMICS, a shiny application for unsupervised cell type deconvolution and biological interpretation of bulk omic data

Abstract Unsupervised deconvolution algorithms are often used to estimate cell composition from bulk tissue samples. However, applying cell type deconvolution and interpreting the results remains a challenge, even more without prior training in bioinformatics. We propose here a tool for estimating and identifying cell type composition from bulk transcriptomes or methylomes. DECOMICS is a shiny-web application dedicated to unsupervised deconvolution approaches of bulk omic data. It provides (i) a variety of existing algorithms to perform deconvolution on the gene expression or methylation-level matrix, (ii) an enrichment analysis module to aid biological interpretation of the deconvolved components, based on enrichment analysis, and (iii) some visualisation tools. Input data can be downloaded in csv format and pre-processed in the web application (normalisation, transformation and feature selection). The results of the deconvolution, enrichment and visualisation processes can be downloaded. DECOMICS is an R-shiny web application that can be launched (i) directly from a local R session using the R package available here https://gitlab.in2p3.fr/Magali.Richard/decomics (either by installing it locally, or via a virtual machine and a Docker image that we provide); or (ii) in the Biosphere—IFB Clouds Federation for Life Science, a multi-cloud environment scalable for high performance computing: Https://biosphere.france-bioinformatique.fr/catalogue/appliance/193/.

Collaboration for new therapies: maximizing health and innovation

IntroductionInnovative medicines and vaccines can provide direct health benefits to patients and populations by preventing, treating and curing diseases, and also drive wider socioeconomic and productivity gains. However, researching and developing them is complex and risky. Funding for life sciences R&D has different sources: public, charitable/NGO, and private sector. We believe there is consensus that all are required, although there is less understanding about their respective roles, synergies, and funding priorities. The purpose of this paper is to provide an overview of the current life sciences innovation ecosystem in Europe, highlighting challenges for funding and innovation of new therapies and our proposed options to address these.MethodsThe basis of this paper stems from the reflections made by the co-authors during a webinar with title “Collaboration for new therapies: maximising funding and innovation,” in March 2023, with further targeted literature reviews.ResultsWe identify eight challenges in the European life sciences ecosystem, some closely related, and nine options that we think might be helpful to address them. Each option on its own can have different levels of ‘impact’, but collectively will provide synergies among them, and thus maximize their impact.DiscussionIt is critical to ascertain how the strengths of each actor can be leveraged to bring new medicines/treatments to market, quicker and more efficiently. We need a trusted environment, with strategic collaborations between the public and private sectors, and policy initiatives and incentives should be targeted to strengthen the infrastructure with the aim of fostering such optimal alliances.

Principles of lipid nanoparticle design for mRNA delivery

AbstractmRNA therapeutics have significantly evolved within the life sciences, particularly in applications such as vaccines, tumor immunotherapy, protein replacement, gene editing, and monoclonal antibody therapy. To fully realize the potential of mRNA drugs and mitigate the adverse effects, substantial vector materials have been developed for delivery of these pharmaceutical agents. Lipid nanoparticles (LNPs) represent the most clinically advanced mRNA carriers, recognized by U.S. Food and Drug Administration approved mRNA vaccines and numerous clinical trials. Diverse therapeutic applications necessitate tailored design of LNPs. Herein, we outline the principles of LNP design for mRNA delivery, focusing specifically on their effectiveness, targeting capabilities, safety profiles, and nanoparticle stability. Additionally, we present the latest advancements in mRNA‐LNP technology. This review aims to elucidate the benefits and design principles of LNP delivery systems for mRNA therapeutics, providing insights into breakthroughs and innovative ideas for further enhancing these advantages. These summaries are dedicated to promoting the broader applications of LNP‐mRNA drugs, aiming to advance the treatment of serious diseases in an effective and safe manner.

Promoting reusable and open methods and protocols (PRO-MaP) can improve methodological reporting in the life sciences

Promoting reusable and open methods and protocols (PRO-MaP) can improve methodological reporting in the life sciences

Culture Level Quotient (CLQ) 2025

The deficiency of today’s science and mathematics becomes obvious from the point of view of the 16 Methods of Reason of Culture Level Quotient (CLQ) of post-science. Post-science has bridged the gap between mathematical and/or logical rigor and reality. The scientific method based on empirical verification is not the only method for discovering knowledge of reality. Methods of reason accept different standards of rigor under different cultures. In particular, social and life sciences involve infinity and permanence, which cannot be empirically verified, and their solutions need to be accepted based on complete mathematical and/or logical rigor. There are 16 distinct methods of reasoning that can be identified and can be used to measure the cultural level of a person or a society. The 16 Methods of Reason are the combination of the 4 basic methods of reasoning: 1) Logic, 2) Mathematics, 3) Empirical Verification, and 4) Faith, each of which has 2 forms: 1) Incomplete and 2) Complete and two types: 1) Exact and 2) Fuzzy. The 16 Methods of Reason are arranged in the order of cultural level from the lowest 1 dealing with problems of lowest complexity to the highest 16 dealing with problems of greatest complexity.

Summary of Varieties and Diversities of Nanomaterials Used in Food Safety and Quality

In all fields of life sciences, the trends toward sustainability, enhanced product safety, and high standards of quality are significant. The food industry uses intelligent packaging to meet these needs. These systems can continuously monitor a product's quality status and notify the customer of any changes. Conventional methods can only satisfy the needs of regular laboratory food analysis. Thus, in the cases of major food safety concerns, quick, economical, and time-saving analysis techniques, including portable, on-site, and home testing kits, are desperately needed. Nonetheless, there is a chance that nanoparticles could be harmful to people's health. Nanotechnology, for instance, can be applied to food processing to improve food's overall quality, including taste, flavor, and bioavailability. It can also help products last longer on the shelf. Moreover, nanotechnology is often applied to food packaging to deliver innovative packaging and serve as an antimicrobial agent. It can offer fresh approaches to thwart fraud and serve as a valuable weapon in our toolbox to prevent bioterrorism. As a result, it is advised to set up a sufficient regulatory framework to control any dangers related to applications of nanotechnology. This review addresses the classification and safety issues involved in the application of nanotechnology in food safety and packaging.

Strategic naturalizing in the Anthropocene: Managing cells, bodies and ecosystems

Discussions on the Anthropocene have called for increased attention to how the effects of human actions on the planet are accounted for. While much of this debate remains at a theoretical level, more studies on situated Anthropocene realities have been called for. Contributing to the latter, this article explores how experimental and clinical interventions are being accounted for in life science laboratories. Drawing on three research cases, genetically modified mosquitoes, laboratory-grown stem cell lines and assisted reproduction in the IVF clinic, the article traces how ‘strategic naturalizing’ is conducted to make sense of and justify human interventions on cells, bodies and ecosystems. Strategic naturalizing in laboratory work is situated, fluid, and also implicates the presence of the social scientist. Although naturalizing biotechnologies is not a new phenomenon, according to our observations scientists increasingly draw on notions of a planet profoundly transformed by human intervention as they conceptualize their own accountability. Consequently, we propose that strategic naturalizing is emerging as an elemental logic in the patchy local enactments of the Anthropocene and its concerns. In the context of experimental and clinical laboratory work, it is a key element in enacting good science and orienting the work towards making biotechnology acceptable in wider society. In studying this, the social scientist also is implicated in situated local enactments of the Anthropocene.

Measuring and understanding information storage and transfer in a simulated human gut microbiome.

Considering biological systems as information processing entities and analyzing their organizational structure via information-theoretic measures has become an established approach in life sciences. We transfer this framework to a field of broad general interest, the human gut microbiome. We use BacArena, a software combining agent-based modelling and flux-balance analysis, to simulate a simplified human intestinal microbiome (SIHUMI). In a first step, we derive information theoretic measures from the simulated abundance data, and, in a second step, relate them to the metabolic processes underlying the abundance data. Our study provides further evidence on the role of active information storage as an indicator of unexpected structural change in the observed system. Besides, we show that information transfer reflects coherent behavior in the microbial community, both as a reaction to environmental changes and as a result of direct effective interaction. In this sense, purely abundance-based information theoretic measures can provide meaningful insight on metabolic interactions within bacterial communities. Furthermore, we shed light on the important however little noticed technical aspect of distinguishing immediate and delayed effects in the interpretation of local information theoretical measures.

Neuropsychological and Health Literacy Correlates of Science Knowledge Among Older and Younger Healthy Adults.

Science knowledge refers to the depth and breadth of facts acquired within the life, social, and earth sciences, and it has implications for both public and personal health. Drawing from cognitive aging theory, we examine whether levels of science knowledge are associated with age, neuropsychological functioning, and personal health literacy. Fifty-two younger and fifty older healthy adults completed our telephone-based study that included a commonly used test of science knowledge, as well as measures of neuropsychological functioning, health literacy, and relevant descriptives (e.g., mood). Adjusting for other demographics and neuropsychological functioning, older adults had significantly lower science knowledge test scores than younger adults. In the full sample, lower science knowledge showed medium-to-large associations with episodic memory, executive functions, and health literacy, independent of years of education. These results suggest that older adults' science knowledge falls slightly below that of their younger counterparts and is independently associated with higher order neuropsychological functions and aspects of personal health, which may have implications for accessing, understanding, and using relevant public health information across the lifespan.

Clinical and genomic features of classical and basal transcriptional subtypes in pancreatic cancer.

Transcriptional profiling of pancreatic cancers (PC) has defined two main transcriptional subtypes, classical and basal. Initial data suggest shorter survival for patients with basal tumors and differing treatment sensitivity to FOLFIRINOX (FFX) and gemcitabine nab-Paclitaxel (GnP) by transcriptional subtype. We examined 8,743 patients with RNA sequencing from PCs performed at Caris Life Sciences (Phoenix, AZ). Classical and basal subtypes were identified using PurIST algorithm on RNA-sequencing and two cohorts were analyzed: (1) Biomarker cohort included patients with complete molecular profiling data (n = 7,250); (2) Outcomes cohort included patients with metastatic disease with available survival outcomes (n=5,335). In the biomarker cohort, 3,063 tumors (42.2%) were strongly classical (SC), and 2,015 tumors (27.8%) were strongly basal (SB). SC and SB tumors showed strong associations with histologic phenotypes and biopsy site. SB tumors had higher rates of KRAS, TP53, and ARID1A mutations, lower rates of SMAD4 mutation, and transcriptional evidence of epithelial mesenchymal transition. Sixty of 77 cases (78%) maintained their transcriptional subtype between temporally and/or spatially disparate lesions. In the outcomes cohort, SB subtype was associated with shorter overall survival time, regardless of whether they received FFX or GnP as first line chemotherapy. Mutant KRAS allele type was prognostic of outcomes, however this impact was restricted to SC tumors, whereas all mutant KRAS alleles had similarly poor outcomes in SB tumors. SB subtype is a strong independent predictor of worse outcomes, irrespective of upfront chemotherapy regimen. Clinical trials should investigate PC transcriptional subtypes as a biomarker.

고교 성취 기준 연계 STEAM 융합 프로그램 개발 및 적용: 체육과 안전 영역 심폐소생술 활용

Objectives The purpose of this study is to develop a STEAM program linked to high school achievement standards based on physical education, life science, and art subjects in the 2015 revised curriculum and apply it to the school field to verify the effectiveness of the program through satisfaction analysis of students and teachers. Methods For the development of the STEAM program linked to subject achievement standards, a total of nine university professors from G Metropolitan City and five middle and high school teachers participated in the program development, and it took about eight months to apply and verify the effectiveness of the program, with three on-site high school teachers participating. As for the learning framework for program development, a total of four instructional plans were developed and applied using the three-step learning framework of “situation presentation-creative design-emotional experience” and then teacher and student satisfaction verification were conducted. Results As a result of this study, first, a STEAM 4th class program was developed that was linked to high school achievement standards based on physical education, life science, and art subjects in the 2015 revised high school curriculum. Second, as a result of the field satisfaction survey after application of the program, it was confirmed that students averaged 3.82 in terms of class satisfaction, class fun, and active participation factors. In the teacher satisfaction survey, significant results were confirmed in the necessity and effectiveness factors of STEAM education, and high satisfaction of 4.0 or more on average was confirmed in both program composition and educational effectiveness factors. Conclusions The development and application of the convergence talent education (TEAM) program using CPR were confirmed, and it was an opportunity to shed new light on the role and function of the ‘physical education subject’ in the development of STEAM convergence classes. In the future, research on the development of STEAM convergence programs in connection with physical education subjects should be actively conducted.

Abstract PR-21: Temporal stability and chemotherapy responsiveness of classical and basal transcriptional subtypes of pancreatic cancer

Abstract Background: Transcriptional profiling of pancreatic cancers (PC) has defined classical and basal subtypes; basal tumors have worse outcomes. Initial data suggest worse outcomes to FOLFIRINOX (FFX) compared with gemcitabine nab-paclitaxel (GnP) in basal tumors. In addition, it is hypothesized that classical to basal conversion may lead to chemotherapy resistance, although clinical evidence for subtype conversion and subtype specific chemotherapy sensitivity are sparse. Here, we examined the temporal stability and clinical implications of PC transcriptional subtypes in a large, real-world dataset. Methods: We examined patients with metastatic PC, who had outcomes data and RNA sequencing (n=5,335) performed at Caris Life Sciences (Phoenix, AZ). Classical and basal subtypes were identified along a six subtype continuum from strong classical (SC) to strong basal (SB) on either pole using PurIST algorithm. Overall survival (OS) was defined from date of biopsy of metastatic site to date of death or last known contact and estimated using Kaplan-Meier method. Survival was compared between groups using log-rank test and cox proportional hazards regression. Predictors of subtype discordance were assessed in patients who underwent RNA-sequencing of two tumor biopsies using multivariable logistic regression. Results: In patients with metastatic PC, SB tumors (n = 1,579) had significantly worse OS compared to SC tumors (n = 2,118), with a median OS of 5.7 vs. 10.0 months, respectively (hazard ratio [HR] 1.49, 95% confidence interval [CI], 1.39-1.60, p = 2.77e-27) independent of impact of age, gender and mutations in KRAS, TP53, CDKN2A or SMAD4 in cox proportional hazard models. OS was worse in patients with SB tumors who received either 1L GnP [SB (n = 112) vs. SC (n = 178), median OS: 6.0 vs. 10.4 months (HR 1.35 [95% CI, 1.05-1.75], p = 0.02)], or 1L FFX [SB (n = 155) vs. SC (n = 215), median OS: 8.9 vs. 12.5 months (HR 1.35 (95% CI, 1.06-1.72), p = 0.013)]. The prognostic impact of transcriptional subtype within different KRAS-mutant alleles is not well defined. OS was short and not significantly different between the three most frequent KRAS alleles (G12 V/D/R) in SB tumors (median OS, KRAS G12R/V/D: 5.4 vs. 5.4 vs. 5.5 months). In SC tumors, KRAS G12D was associated with a significantly worse OS compared to KRAS G12R (median OS: 8.6 vs. 11.9 months, HR 1.23 (95% CI, 1.04-1.47), p = 0.018). KRAS G12V had a numerically worse survival compared with KRAS G12R in SC tumors (median OS: 9.4 vs. 11.9 months, HR 1.15 (95% CI, 0.96-1.37), p = 0.12). Sixty of 77 cases (78%) maintained their transcriptional subtype between two temporally &/or spatially disparate lesions. The likelihood of transcriptional subtype change was independent of the duration between (p = 0.79) or site of (p = 0.37) the two biopsies. Conclusions: SB subtype is a strong independent predictor of worse outcomes, irrespective of mutant KRAS allele or upfront chemotherapy regimen, and tends to remain stable between biopsies in individual patients Citation Format: Harshabad Singh, Joanne Xiu, Kevin Kapner, Chen Yuan, Raja R Narayan, Matthew Oberley, Alex Farrell, Rishi Surana, Brandon M Huffmann, Kimberly J Perez, James M Cleary, Alexander C Jordan, Andressa Dias Costa, Hannah L Williams, Srivatsan Raghavan, Benjamin Weinberg, Michael J Pishvaian, Rachna T Shroff, Sanjay Goel, Stephanie K Dougan, Jonathan Nowak, David Spetzler, George Sledge, Brian M Wolpin, Andrew J Aguirre. Temporal stability and chemotherapy responsiveness of classical and basal transcriptional subtypes of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr PR-21.

Synthesis of Axially Chiral Monofluoroalkenes via Nickel-Catalyzed Reductive Cross-Coupling of gem-Difluoroalkenes.

Enantioenriched monofluoroalkenes are important structural motifs in life science and functional materials. To date, only limited strategies were reported for the synthesis of monofluoroalkenes with stereogenic carbon centers; the axially chiral counterpart is still highly desirable. Herein, we report Ni-catalyzed defluorinative cross-electrophile coupling of gem-difluoroalkenes with biaryl electrophiles for the synthesis of axially chiral monofluoroalkenes. The resulting axially chiral monofluoroalkenes are formed with excellent regio- and stereoselectivities. Synthetic transformation of these axially enantioenriched monofluoroalkenes was also demonstrated.

Design and synthesis of a 2,5-Diarylthiophene chromophore for enhanced near-infrared two-photon uncaging efficiency of calcium ions.

The design and synthesis of two-photon-responsive chromophores have recently garnered significant attention owing to their potential applications in materials and life sciences. In this study, a novel π-conjugated system, 2-dimethylaminophenyl-5-nitrophenylthiophene derivatives, featuring a thiophene unit as the π-linker between the donor (NMe2C6H4-) and acceptor (NO2C6H4-) units was designed, synthesized, and applied for the development of two-photon-responsive chromophores as a photoremovable protecting group in the near-infrared region. Notably, the positional effect of the nitro group (NO2), meta versus para position, was observed in the uncaging process of benzoic acid. Additionally, while the para-isomer exhibited a single fluorescence peak, a dual emission was detected for the meta-isomer in polar solvents. The caged calcium ion (Ca2+) incorporating the newly synthesized thiophene unit exhibited a sizable two-photon absorption cross-section value (σ2 = 129 GM at 830nm). Both one-photon and two-photon photoirradiation of caged calcium ions successfully released calcium ions, indicating the potential utility of 2,5-diarylthiophene derivatives in future biological studies.

PULSE Ambassadors program: empowering departments to transform STEM education for inclusion and student success.

The Partnership for Undergraduate Life Sciences Education (PULSE) is a non-profit educational organization committed to promoting the transformation of undergraduate STEM education by supporting departments in removing barriers to access, equity, and inclusion and in adopting evidence-based teaching and learning practices. The PULSE Ambassadors Campus Workshop program enables faculty and staff members of host departments to 1) develop communication, shared leadership, and inclusion skills for effective team learning; 2) implement facilitative leadership skills (e.g., empathic listening and collaboration); 3) create a shared vision and departmental action plan; and 4) integrate diversity, equity, and inclusion practices in the department and curriculum. From the first workshop in 2014, teams of trained Ambassadors conducted workshops at 58 institutions, including associate, bachelor, master, and doctoral institutions. In their workshop requests, departments cited several motivations: desire to revise and align their curriculum with Vision and Change recommendations, need for assistance with ongoing curricular reform, and wish for external assistance with planning processes and communication. Formative assessments during and immediately following workshops indicated that key outcomes were met. Post-workshop interviews of four departments confirm progress achieved on action items and development of individual department members as agents of change. The PULSE Ambassadors program continues to engage departments to improve undergraduate STEM education and prepare departments for the challenges and uncertainties of the changing higher education landscape.

How to introduce a new bacteriophage on the block: a short guide to phage classification.

Bacteriophage (phage) studies established the field of molecular biology and continue to propel life science research forward due to their diversity, abundance, and potential applications. In this Gem article, we orient newcomers to four common ways phages are currently classified: infection cycle, morphology, taxonomy, and supergroup. By using these classifications, researchers can determine where any novel phage fits into the scheme of the known "phage-verse".

The global geography of artificial intelligence in life science research

Artificial intelligence (AI) promises to transform medicine, but the geographic concentration of AI expertize may hinder its equitable application. We analyze 397,967 AI life science research publications from 2000 to 2022 and 14.5 million associated citations, creating a global atlas that distinguishes productivity (i.e., publications), quality-adjusted productivity (i.e., publications stratified by field-normalized rankings of publishing outlets), and relevance (i.e., citations). While Asia leads in total publications, Northern America and Europe contribute most of the AI research appearing in high-ranking outlets, generating up to 50% more citations than other regions. At the global level, international collaborations produce more impactful research, but have stagnated relative to national research efforts. Our findings suggest that greater integration of global expertize could help AI deliver on its promise and contribute to better global health.

Drosophila are hosts to the first described parasitoid wasp of adult flies.

Parasitoid wasps are exceptionally diverse and use specialized adaptations capable of manipulating the physiology and behaviour of host organisms1. In more than two centuries since the first records of Drosophila-parasitizing wasps, nearly 200 described and provisional parasitoid species of drosophilids have been identified2. These include endoparasitoids and ectoparasitoids, as well as species attacking larval and pupal hosts3. Despite a deep history of research attention and remarkable biodiversity, a wasp species that attacks and develops inside the adult stage of a fly host has not been described previously. Here we report the discovery of a wasp species that infects the adult stage of fruit flies in the genus Drosophila, including one of the most deeply studied model organisms in biology, Drosophila melanogaster. Notably, this wasp can be easily collected from backyard fly baits and has a broad geographic distribution throughout the eastern USA. We document its life history and unique host interactions, including egg-laying into and larval emergence from adult flies, and provide protocols to raise wasps from wild-caught host flies. Our results emphasize the need for ongoing research investment in insect biodiversity and systematics. As parasitoid research continues to uncover unusual biology and supports fundamental mechanistic insights into immunity4, metabolism5, ecology6, evolution7-9 and behaviour10-12, we anticipate that this wasp's association with the laboratory model organism, D. melanogaster, will provide new research opportunities across the life sciences.

Artificial Intelligence in Medical Affairs: A New Paradigm with Novel Opportunities.

The advent of artificial intelligence (AI) revolutionizes the ways of working in many areas of business and life science. In Medical Affairs (MA) departments of the pharmaceutical industry AI holds great potential for positively influencing the medical mission of identifying and addressing unmet medical needs and care gaps, and fostering solutions that improve the egalitarian and unbiased access of patients to treatments worldwide. Given the essential position of MA in corporate interactions with various healthcare stakeholders, AI offers broad possibilities to support strategic decision-making and to pioneer novel approaches in medical stakeholder interactions. By analyzing data derived from the healthcare environment and by streamlining operations in medical content generation, AI advances data-based prioritization and strategy execution. In this review, we discuss promising AI-based solutions in MA that support the effective use of heterogenous information from observations of the healthcare environment, the enhancement of medical education, and the analysis of real-world data. For a successful implementation of such solutions, specific considerations partly unique to healthcare must be taken care of, for example, transparency, data privacy, healthcare regulations, and in predictive applications, explainability.

Improved Visual Saliency of Graph Clusters with Orderable Node-Link Layouts.

Graphs are often used to model relationships between entities. The identification and visualization of clusters in graphs enable insight discovery in many application areas, such as life sciences and social sciences. Force-directed graph layouts promote the visual saliency of clusters, as they bring adjacent nodes closer together, and push non-adjacent nodes apart. At the same time, matrices can effectively show clusters when a suitable row/column ordering is applied, but are less appealing to untrained users not providing an intuitive node-link metaphor. It is thus worth exploring layouts combining the strengths of the node-link metaphor and node ordering. In this work, we study the impact of node ordering on the visual saliency of clusters in orderable node-link diagrams, namely radial diagrams, arc diagrams and symmetric arc diagrams. Through a crowdsourced controlled experiment, we show that users can count clusters consistently more accurately, and to a large extent faster, with orderable node-link diagrams than with three state-of-the art force-directed layout algorithms, i.e., 'Linlog', 'Backbone' and 'sfdp'. The measured advantage is greater in case of low cluster separability and/or low compactness.