OniX Hub

06/05/2024

Major cause of inflammatory bowel disease found

Scientists have found a weak spot in our DNA that is present in 95% of people with the disease.

05/17/2024

Highly pathogenic avian influenza viruses of the H5N1 clade 2.3.4.4b were detected in North America in the winter of 2021/2022. These viruses have spread across the Americas, causing morbidity and mortality in both wild and domestic birds as well as some mammalian species, including cattle. Many surveillance programs for wildlife as well as commercial poultry operations have detected these viruses. In this study, we conducted surveillance of avian species in the urban environment in New York City. We detected highly pathogenic H5N1 viruses in six samples from four different bird species and performed whole-genome sequencing. Sequencing analysis showed the presence of multiple different genotypes. Our work highlights that the interface between animals and humans that may give rise to zoonotic infections or even pandemics is not limited to rural environments and commercial poultry operations but extends into the heart of our urban centers.

While surveillance programs for avian influenza viruses are often focused on migratory routes and their associated stop-over locations or commercial poultry operations, many bird species—including migratory birds—frequent or live in urban green spaces and ...

05/17/2024

The biotech industry is witnessing a stark paradox in 2024. On one hand, there’s a group of biotech startups that are thriving, attracting nearly $3 billion in funding in Q1 2024 alone.

More than 11,000biotech and pharma workers lost jobs in the first four months of 2024, with Big Pharma behind the majority.

05/14/2024

Our study confirms and uncovers new LRRK2 associations in IBD-PD. The identification of novel inflammation and autophagy-related genes supports and expands previous findings related to IBD-PD pathogenesis, and underscores the significance of therapeutic interventions for reducing systemic inflammation.

Background Inflammatory bowel disease (IBD) and Parkinson’s disease (PD) are chronic disorders that have been suggested to share common pathophysiological processes. LRRK2 has been implicated as playing a role in both diseases. Exploring the genetic basis of the IBD-PD comorbidity through studying...

05/08/2024

A key challenge in drug discovery is to optimize, in silico, various absorption and affinity properties of small molecules. One strategy that was proposed for such optimization process is active learning. In active learning molecules are selected for testing based on their likelihood of improving model performance. To enable the use of active learning with advanced neural network models we developed two novel active learning batch selection methods. These methods were tested on several public datasets for different optimization goals and with different sizes. We have also curated new affinity datasets that provide chronological information on state-of-the-art experimental strategy. As we show, for all datasets the new active learning methods greatly improved on existing and current batch selection methods leading to significant potential saving in the number of experiments needed to reach the same model performance. Our methods are general and can be used with any package including the popular DeepChem library.

A key challenge in drug discovery is to optimize, in silico, various absorption and affinity properties of small molecules. One strategy that was proposed for such optimization process is active learning. In active learning molecules are selected for testing based on their likelihood of improving mo...

05/07/2024

Shifts in the magnitude and nature of gut microbial metabolites have been implicated in Alzheimer’s disease (AD), but the host receptors that sense and respond to these metabolites are largely unknown. Here, we develop a systems biology framework that integrates machine learning and multi-omics to identify molecular relationships of gut microbial metabolites with non-olfactory G-protein-coupled receptors (termed the “GPCRome”). We evaluate 1.09 million metabolite-protein pairs connecting 408 human GPCRs and 335 gut microbial metabolites. Using genetics-derived Mendelian randomization and integrative analyses of human brain transcriptomic and proteomic profiles, we identify orphan GPCRs (i.e., GPR84) as potential drug targets in AD and that triacanthine experimentally activates GPR84. We demonstrate that phenethylamine and agmatine significantly reduce tau hyperphosphorylation (p-tau181 and p-tau205) in AD patient induced pluripotent stem cell-derived neurons. This study demonstrates a systems biology framework to uncover the GPCR targets of human gut microbiota in AD and other complex diseases if broadly applied.

https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00456-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221112472400456X%3Fshowall%3Dtrue

05/07/2024

Shifts in the magnitude and nature of gut microbial metabolites have been implicated in Alzheimer’s disease (AD), but the host receptors that sense and respond to these metabolites are largely unknown. Here, we develop a systems biology framework that integrates machine learning and multi-omics to identify molecular relationships of gut microbial metabolites with non-olfactory G-protein-coupled receptors (termed the “GPCRome”). We evaluate 1.09 million metabolite-protein pairs connecting 408 human GPCRs and 335 gut microbial metabolites. Using genetics-derived Mendelian randomization and integrative analyses of human brain transcriptomic and proteomic profiles, we identify orphan GPCRs (i.e., GPR84) as potential drug targets in AD and that triacanthine experimentally activates GPR84. We demonstrate that phenethylamine and agmatine significantly reduce tau hyperphosphorylation (p-tau181 and p-tau205) in AD patient induced pluripotent stem cell-derived neurons. This study demonstrates a systems biology framework to uncover the GPCR targets of human gut microbiota in AD and other complex diseases if broadly applied.

Combining machine learning and multi-omics analysis, Qiu et al. identify the molecular relationship between gut metabolites and dark G-protein-coupled receptors (GPCRome) in Alzheimer’s disease. This study offers a powerful systems biology resource to identify microbiome-targeted therapies via ta...

05/07/2024

Various gut bacteria, including Lactobacillus plantarum, possess several enzymes that produce hydroxy fatty acids (FAs), oxo FAs, conjugated FAs, and partially saturated FAs from polyunsaturated FAs as secondary metabolites. Among these derivatives, we identified 10-oxo-cis-6,trans-11-octadecadienoic acid (γKetoC), a γ-linolenic acid (GLA)-derived enon FA, as the most effective immunomodulator, which inhibited the antigen-induced immunoactivation and LPS-induced production of inflammatory cytokines. The treatment with γKetoC significantly suppressed proliferation of CD4+ T cells, LPS-induced activation of bone marrow-derived dendritic cells (BMDCs), and LPS-induced IL-6 release from peritoneal cells, splenocytes, and CD11c+ cells isolated from the spleen. γKetoC also inhibited the release of inflammatory cytokines from BMDCs stimulated with poly-I:C, R-848, or CpG. Further in vitro experiments using an agonist of GPR40/120 suggested the involvement of these GPCRs in the effects of γKetoC on DCs. We also found that γKetoC stimulated the NRF2 pathway in DCs, and the suppressive effects of γKetoC and agonist of GPR40/120 on the release of IL-6 and IL-12 were reduced in Nrf2-/- BMDCs. We evaluated the role of NRF2 in the anti-inflammatory effects of γKetoC in a dextran sodium sulfate-induced colitis model. The oral administration of γKetoC significantly reduced body weight loss, improved stool scores, and attenuated atrophy of the colon, in wild-type C57BL/6 and Nrf2+/- mice with colitis. In contrast, the pathology of colitis was deteriorated in Nrf2-/- mice even with the administration of γKetoC. Collectively, the present results demonstrated the involvement of the NRF2 pathway and GPCRs in γKetoC-mediated anti-inflammatory responses.

Various gut bacteria, including Lactobacillus plantarum, possess several enzymes that produce hydroxy fatty acids (FAs), oxo FAs, conjugated FAs, and partial...

05/03/2024

May 3, 2024 - Harnessing Generative AI to Amplify Patient Voices in Drug Development.

The development of new drugs is a challenging process, involving substantial investments of time, resources, and expertise. However, one crucial stakeholder group is often overlooked or underutilized in this process: the patients themselves, along with their caregivers, families, and friends. These stakeholders possess a unique and invaluable perspective on the disease, its impact on daily life, and the unmet needs that drive the search for new therapeutic solutions.

This white paper explores how generative AI can facilitate the critical role that patients play throughout the drug development journey, from idea and target identification to product launch and post-marketing surveillance. By embracing a patient-centric approach powered by generative AI, stakeholders can gain deeper insights into the real-world challenges faced by those living with the disease, identify key symptoms and priorities, and develop treatments that truly address their needs.

The development of new drugs is a challenging process, involving substantial investments of time, resources, and expertise. However, one crucial stakeholder group is often overlooked or underutilized in this process: the patients themselves, along with their caregivers, families, and friends. These....

05/02/2024

The U.S. National Science Foundation has launched a $9.5 million research funding opportunity in partnership with BASF, Dow, IBM, PepsiCo Inc. and Procter & Gamble Co. Sustainable Polymers Enabled by Emerging Data Analytics (SPEED) is part of NSF's Molecular Foundations for Sustainability program and seeks to accelerate the discovery and manufacture of superior and sustainable polymers to enhance national competitiveness and tackle global challenges such as plastic waste. NSF is providing $7 million, and the five industry partners are collectively contributing $2.5 million in funding and in-kind donations.

The U.S. National Science Foundation has launched a $9.5 million research funding opportunity in partnership with BASF, Dow, IBM, PepsiCo Inc. and Procter &…