📣 New Article from Network and Systems Medicine on #ScienceOpen!
🆕📄 'Identification of Transcriptional Regulators Using a Combined Disease Module Identification and Prize-Collecting Steiner Tree Approach' ➡️ https://drugrepocentral.scienceopen.com/hosted-document?doi=10.14293/NSM.25.1.0003
#REPO4EU #NetworkMedicine #Bioinformatics #TranscriptionFactors
Identification of Transcriptional Regulators Using a Combined Disease Module Identification and Prize-Collecting Steiner Tree Approach
<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d4991e168">Transcription factors play important roles in maintaining normal biological function,
and their dysregulation can lead to the development of diseases. Identifying candidate
transcription factors involved in disease pathogenesis is thus an important task for
deriving mechanistic insights from gene expression data. We developed Transcriptional
Regulator Identification using Prize-collecting Steiner trees (TRIPS), a workflow
for identifying candidate transcriptional regulators from case–control expression
data. In the first step, TRIPS combines the results of differential expression analysis
with a disease module identification step to retrieve perturbed subnetworks comprising
an expanded gene list. TRIPS then solves a prize-collecting Steiner tree problem on
a gene regulatory network, thereby identifying candidate transcriptional modules and
transcription factors. We compare TRIPS to relevant methods using publicly available
disease datasets and show that the proposed workflow can recover known disease-associated
transcription factors with high precision. Network perturbation analyses demonstrate
the reliability of TRIPS results. We further evaluate TRIPS on Alzheimer’s disease,
diabetic kidney disease, and prostate cancer single-cell omics datasets. Overall,
TRIPS is a useful approach for prioritizing transcriptional mechanisms for further
downstream analyses.
</p>
'Enhancing the Accuracy of Network Medicine Through Understanding the Impact of Sample Size in Gene Co-expression Networks' - a Network and Systems Medicine published article on #ScienceOpen 📄🔓
➡️ https://drugrepocentral.scienceopen.com/hosted-document?doi=10.14293/NSM.25.1.0002
#REPO4EU #NetworkMedicine #SampleSizeMatters #GeneCoexpression #OpenAccess
Enhancing the Accuracy of Network Medicine Through Understanding the Impact of Sample Size in Gene Co-expression Networks
<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d3821688e235">Network medicine relies on RNA sequencing to infer gene co-expression networks, which
are crucial to identify functional gene clusters and gene regulatory interactions,
and offer a deeper understanding of disease phenotypes and drug mechanisms. It remains
unknown, however, how many samples do we need to make reliable predictions. Here,
we propose a power-law model to predict the relationship between the number of inferred
significant interactions and sample size, allowing us to quantitatively link sample
size to the accuracy of the inferred networks. We apply our model to investigate the
effect of sample size on biomarker discovery and differentiation of protein–protein
interactions from non-interacting pairs, ultimately unveiling the critical role of
data quality in generating meaningful predictions in network medicine.
</p>
'Multi-omic Signatures Relate to the Severity of Pulmonary Outcome in Neonates Traced into Adult Disease' - a Network and Systems Medicine published article on #ScienceOpen 📄🔓
➡️ https://drugrepocentral.scienceopen.com/hosted-document?doi=10.14293/NSM.25.1.0001
#REPO4EU #BronchopulmonaryDysplasia #MultiOmics #Biomarkers #PrecisionMedicine
Multi-omic Signatures Relate to the Severity of Pulmonary Outcome in Neonates Traced into Adult Disease
<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d2658128e278">Chronic lung disease (CLD) i.e., bronchopulmonary dysplasia (BPD) is the most common
long-term complication after preterm birth. This clinically heterogeneous disease
is characterized by impaired development of the gas exchange area and the bronchial
tree. The identification of disease endotypes or indicators of disease onset early
after birth would allow for individualized monitoring and treatment. In a cohort of
55 preterm infants phenotypically described by detailed clinical data on pregnancy,
birth, and neonatal intensive care unit care until discharge, and a complete assessment
of pulmonary and extrapulmonary morbidities, we analyzed 1120 proteins and 213 metabolites
in samples obtained in the first weeks of life to characterize biological signatures
of BPD. Latent factor analysis highlighted seven factors, three of which linked proteomic
and metabolomic data, highlighting a common inflammatory/immune signature but no independent
endotypes. We next used abundance patterns of differentially abundant proteins and
metabolites and successfully identified biomarker candidates associated with disease
severity including PC(O-36:5), CCL22, KIR3DL2, SCGF-alpha, and SCGF-beta. Confirmation
of the discriminatory power of these biomarkers in adult CLD patients (n=44) using
matched proteomic profiling suggests CCL22, KIR3DL2, and SCGF-beta as shared biomarker
candidates of BPD and adult CLD.
</p>
Network and Systems Medicine is a 💎 #OpenAccess, peer-reviewed journal focused on interdisciplinary approaches that leverage the power of big data through #NetworkScience and #SystemsThinking in #Medicine. 🕸️🧠🩺 #REPO4EU
➡️ https://drugrepocentral.scienceopen.com/collection/NetMed
Network and Systems Medicine
<p><strong><em>Network and Systems Medicine </em></strong>is an open access, peer-reviewed journal focused on interdisciplinary approaches to exploiting the power of big data by applying network science and systems thinking to medicine. <strong><em>Network and Systems Medicine</em></strong> yields major breakthroughs towards mechanism-based re-definitions of diseases for high-precision diagnostics and treatments, proof-of-concept trials, confirmatory trials, pharmacoepidemiology.</p><p><strong>e-ISSN:</strong> 2941-251X</p>
RePo-SUDOE: A Transnational Network for Drug Repurposing in the SUDOE Space
<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d13493990e380">The development of new drugs is hindered by high failure rates, substantial costs,
and prolonged timelines, highlighting the importance of drug repurposing (or drug
repositioning) as a key strategy to identify new therapeutic applications for existing
drugs. Despite its potential, collaboration within the SUDOE space, concerning Portugal,
Spain, and France, remains limited, as evidenced by a bibliometric analysis that reveals
their relatively modest contribution to global drug repurposing research in comparison
to leading countries, such as China, USA, and UK. The RePo-SUDOE project aims to address
this gap by bringing together diverse partners to advance drug repurposing technologies
and enhance the region’s competitiveness in this field. The project includes three
key objectives: (i) raising awareness and understanding of drug repurposing technologies,
positioning SUDOE’s R&D centers as leaders in European research; (ii) fostering multidisciplinary
collaboration and identifying opportunities for innovative drug repurposing initiatives
across the SUDOE space through the establishment of a transnational network with a
key focus of developing methodologies for drug repurposing for cancer treatment; (iii)
creating a prototype of a three-dimensional visualization room for biological systems
with virtual and augmented reality technologies to explore drug–target interactions,
engaging STEAM students and researchers in immersive learning. The RePo-SUDOE project
brings together diverse partners from the SUDOE space to collaborate on drug repurposing,
making scientific information more accessible, and using advanced visualization technologies
to strengthen the field in this geographic region.
</p>
"Manhattan Projects for Preventive Medicine" - a brand new article from Network and Systems Medicine Journal from #REPO4EU on #ScienceOpen 💊 🆕
🖇️ #PreventiveMedicine #ChronicDisease #ManhattanProject
International Drug Repurposing Patent Landscaping, Part 3: Chronic Neurodegenerative Diseases 2010–2024
<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d12346086e95">This study presents a comprehensive landscape of international drug repurposing patent
applications published between January 2010 and December 2024, encompassing four chronic
neurodegenerative disease groups of major societal and economic significance: Alzheimer’s
disease and related primary dementias (49 documents), Parkinson’s disease (22 documents),
multiple sclerosis (25 documents), and peripheral neuropathies (13 documents). The
analysis was restricted to patent applications that disclosed supporting experimental
data. Patent publication activity remained relatively stable throughout the 15-year
investigation period, with the exception of a modest decline during 2021–2023, likely
reflecting the impact of the coronavirus disease 2019 (Covid-19) pandemic. Our analysis
reveals agents from a remarkable diversity of therapeutic classes being claimed for
repurposing, predominantly targeting pharmacological mechanisms distinct from those
underlying their original approved indications. Although none of the repurposed agents
identified in this landscape has yet received regulatory approval for these neurodegenerative
indications, this patent-based analysis provides unique insights into repurposing
activities in therapeutically challenging conditions from an intellectual property
perspective that substantially differs from findings reported in the peer-reviewed
literature.
</p>
Extracellular vesicle-associated transcriptomic and proteomic biomarkers show in vitro potential for vandetanib treatment monitoring in anaplastic thyroid cancer
<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d660062e280">
<b>Background: </b>Anaplastic thyroid cancer (ATC) is an aggressive and rare disease. Rapid metastasis
and limited treatments call for additional therapeutic options, including drug repurposing.
The early spreading of ATC highlights the importance of rapid therapy success assessment,
which could be achieved by measurement of extracellular vesicle (EV)-associated cell-free
RNA in liquid biopsy samples. Recent studies have discovered the potential of the
receptor tyrosine kinase inhibitor vandetanib for ATC treatment
<i>in vitro</i> and
<i>in vivo</i>. Given the rarity of ATC patients receiving off-label vandetanib treatment, acquiring
patient samples for clinical studies is a prolonged process, and pre-clinical investigations
are needed to elucidate the effects of vandetanib on ATC cells.
</p><p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d660062e291">
<b>Objective:</b> Here, we present an
<i>in vitro</i> study addressing holistic transcriptional and proteomic changes induced in the ATC
cell line Cal62 by three doses of vandetanib and quantified by high-throughput methods.
</p><p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d660062e299">
<b>Methods:</b> By comparing the transcriptional and proteomic data sets and applying dimensional
reduction models such as sparse partial least-squares discriminant analysis, we refined
a set of 21 biomarker candidates.
</p><p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d660062e304">
<b>Results:</b> Out of these, we report a final signature of eight transcriptional biomarkers, validated
in cellular and cell-free RNA by RT-qPCR and verified for biological significance
and discriminatory power by pathway over-representation analysis and partial least-squares
regression. This transcriptional biomarker signature can distinguish vandetanib treatment
from control in cell-free RNA isolated from Cal62 EVs and can be measured reliably,
easily, and quickly using RT-qPCR.
</p><p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dir="auto" id="d660062e309">
<b>Conclusions:</b> Our findings may serve as a basis for future clinical trials with liquid biopsy samples
from ATC patients undergoing off-label vandetanib treatment.
</p>
DrugRxiv
<p>A preprint server dedicated to the needs of the Drug Repurposing community</p>
Repositioning antivirals against COVID-19: Synthetic pathways, mechanisms, and therapeutic insights.
<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d6481623e211">The pandemic of COVID-19 has ignited a global race to locate effective therapies with
drug repositioning emerging as a leading strategy due to its cost-effectiveness and
established safety profiles. Remdesivir, Favipiravir, Hydroxychloroquine, and Chloroquine
have been the focus of rigorous clinical trials to determine their therapeutic potential
against SARS-CoV-2. This article delves into the innovative synthetic strategies behind
these drugs, providing a blueprint for researchers navigating the complex landscape
of antiviral development. Beyond synthesis, we explore the fascinating mechanisms
of action: hydroxychloroquine and chloroquine elevate lysosomal pH to impede autophagy
and viral replication; favipiravir, a nucleoside analogue, induces lethal mutagenesis
or RNA chain termination and remdesivir disrupts viral RNA synthesis through delayed
chain termination. By merging synthetic methodologies with mechanistic insights, this
article offers a comprehensive resource aimed at accelerating the development of potent
COVID-19 therapies and underscores the crucial part that chemistry in addressing global
health emergencies. It also underscores the vital function of chemistry in addressing
global health emergencies and highlights how innovative drug design and repurposing
can provide rapid responses to emerging infectious diseases. This fusion of chemistry
and virology not only advances our understanding of drug action but also paves the
way for the discovery of new therapeutic agents crucial in future pandemics.
</p>
ScienceOpen