imagine (Institute of molecular genetics and genetic engineering)
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Exploration of Intrinsic Disorder Regions through Classification of Intrinsically Disordered Proteins Using PPI Network Structure and Sequence Attributes: A Case Study
In this study, the prediction of Intrinsically Disordered Proteins (IDPs) was explored
by utilizing the structure of Protein-Protein Interaction (PPI) networks and sequence
characteristics. A weighted PPI network, where edge weights represented gene coexpression
information between two proteins, was used to extract attributes related
to protein topological properties via the node2vec+ tool. Additionally, attributes derived
from primary sequence information were incorporated, focusing on amino acid properties
such as order/disorder promotion (Type A attributes) and physicochemical properties
including aromatic/aliphatic, polar/non-polar, non-zero/zero, hydrophobic/hydrophilic,
and positive/negative (Type B attributes).
Proteins were classified into IDP and non-IDP categories using a K-Nearest Neighbors (KNN)
classifier under four scenarios: (1) based solely on network attributes, (2) incorporating
network attributes and sequence Type A attributes, (3) incorporating network attributes
and sequence Type B attributes, and (4) considering network attributes along with both
sequence Type A and Type B attributes. Proteins misclassified as IDPs in these scenarios
were further examined using the IUPred2 tool, which revealed that only a subset of these
proteins indeed possessed intrinsic disorder regions (IDRs) along their sequences.
This study was conducted as a case study using the PPI network model of the yeast
organism from the BioGRID database, with the list of yeast IDP proteins sourced from the
DisProt database. Gene co-expression information was obtained using the SPELL tool.In this study, the prediction of Intrinsically Disordered Proteins (IDPs) was explored
by utilizing the structure of Protein-Protein Interaction (PPI) networks and sequence
characteristics. A weighted PPI network, where edge weights represented gene coexpression
information between two proteins, was used to extract attributes related
to protein topological properties via the node2vec+ tool. Additionally, attributes derived
from primary sequence information were incorporated, focusing on amino acid properties
such as order/disorder promotion (Type A attributes) and physicochemical properties
including aromatic/aliphatic, polar/non-polar, non-zero/zero, hydrophobic/hydrophilic,
and positive/negative (Type B attributes).
Proteins were classified into IDP and non-IDP categories using a K-Nearest Neighbors (KNN)
classifier under four scenarios: (1) based solely on network attributes, (2) incorporating
network attributes and sequence Type A attributes, (3) incorporating network attributes
and sequence Type B attributes, and (4) considering network attributes along with both
sequence Type A and Type B attributes. Proteins misclassified as IDPs in these scenarios
were further examined using the IUPred2 tool, which revealed that only a subset of these
proteins indeed possessed intrinsic disorder regions (IDRs) along their sequences.
This study was conducted as a case study using the PPI network model of the yeast
organism from the BioGRID database, with the list of yeast IDP proteins sourced from the
DisProt database. Gene co-expression information was obtained using the SPELL tool
The influence of genetic variations on the late effects in childhood cancer survivors
Childhood cancer survivors represent a unique and constantly growing population that, although being
cured from primary cancer, carries a substantial risk for long-term morbidity and premature mortality.
The inter-individual variability in the frequency and severity of treatment-related late complications
suggests the role of genetic factors. A better understanding of genetic modifiers for late effects after
childhood cancer could have a significant impact on future survivorship research and care. This could
facilitate the implementation of novel strategies to reduce the burden of therapy-related late toxicities
and improve quality of life for childhood cancer survivors
Zebrafish ankrd1a as a common player in heart regeneration and skeletal muscle repair
In contrast to humans, zebrafish have a remarkable ability to regenerate their hearts after injury, while both humans and zebrafish efficiently repair the wounded skeletal muscle. Common players in these two processes might represent potential targets for the development of efficient therapies to stimulate human heart to regenerate after injury. We identified ankrd1a expression to be upregulated in both regenerating zebrafish hearts and in repairing skeletal muscle. Its mammalian homolog ANKRD1/CARP encodes a stress responsive cardiac ankyrin repeat protein involved in transcriptional regulation, sarcomere assembly and mechanosensing. Using a TgBAC(ankrd1a:EGFP) line, we showed that activation of ankrd1a in cryoinjured heart is restricted to border zone cardiomyocytes, implicating this gene in dedifferentiation and proliferation of regenerating cardiomyocytes. After stab wound injury of skeletal muscle expression of the fluorescent reporter was observed from 3 dpi, when new EGFP-positive muscle cells emerged inside the injury zone. At later time points, EGFP-positive myofibers were visible in the deeper tissue layers, concomitant with active repair of the injured tissue. In cryoinjured skeletal muscle, strong activation of ankrd1a was also observed in myofibers adjacent to the injury, and in those on uninjured side. Detection of the transgene in both newly formed myofibers that invade the wound and in the apparently uninjured tissue surrounding the injury suggests the role of ankrd1a in skeletal muscle tissue repair and adaptive processes in uninjured myofibers surrounding the injury site. Our results implicate ankrd1a in zebrafish muscle regeneration, repair and remodeling, promoting it as an attractive target for translational studies, as a player in muscle healing and as a sensor of stressed muscle.10th Strategic Conference of Zebrafish Investigators, January 6-9, 2024 at the Asilomar Conference Grounds in Pacific Grove, Californi
Better real-world health-data distributed analytics research platform
In recent years, data-driven medicine has gained increasing importance in terms of diagnosis,
treatment, and research due to the exponential growth of healthcare data. The linkage of cross-
border health data from various sources, including genomics, and analysis via innovative
approaches based on artificial intelligence (AI) will enable a better understanding of risk factors,
causes, and the development of optimal treatment in different disease areas. Nevertheless, the
reuse of patient data is often limited to datasets available at a single medical centre. The main
reasons why health data is not shared across institutional borders rely on ethical, legal, and privacy
aspects and rules. Therefore, in order to (1) enable health data sharing across national borders,
(2) fully comply with present GDPR privacy guidelines / regulations and (3) innovate by pushing
research beyond the state of the art, BETTER proposes a robust decentralised privacy-preserving
infrastructure which will empower researchers, innovators and healthcare professionals to exploit
the full potential of larger sets of multi-source health data via tailored made AI tools useful to
compare, integrate, and analyse in a secure, cost-effective fashion; with the very final aim of
supporting the improvement of citizen’s health outcomes. In detail, this interdisciplinary project
proposes the co-creation of 3 clinical use cases involving 7 medical centres located in the EU and
beyond, where sensitive patient data, including genomics, are made available and analysed in a
GDPR-compliant mechanism via a Distributed Analytics (DA) paradigm called the Personal Health
Train (PHT). The main principle of the PHT is that the analytical task is brought to the data provider
(medical centre) and the data instances remain in their original location. In this project, two
mature implementations of the PHT (PADME and Vantage6) already validated in real-world
scenarios will be fused together to build the BETTER platform.Principal Investigator: Dr. Matteo Bregonzio, DATRIXCoordinator for IMGGE: Dr. Maja StojiljkovićDuration period: 2024-202
Diabetic chronic wounds prevention and eradication – patients come to the rescue
Chronic wounds (CWs) are a frequent complication of diabetes occurring in 25% of individuals.
They are responsible for 60% of non-traumatic limb amputations. The chronicity of these wounds
is attributed to a continuous presence of bacterial infection. The project will use synergy between
people suffering from diabetes, healthcare workers, and researchers to identify lifestyle factors
that contribute to the development of CWs. Diabetic participants will identify lifestyle factors
contributing to CW development and further correlation of those factors with microbial
composition in wounds will be tested by researchers. Patients will be trained to work on data
acquisition and results communication and be presented with data management. Outcomes of
the project will improve the quality of life, increase personal agency, raise awareness about the
problem, prompt research toward development of more efficient therapeutics and strive to
change guidelines for diabetic wound treatment.Principal Investigator: Dr. Miloš RokićCoordinator for IMGGE: Dr. Ivana Morić, Dr. Lidija ŠenerovićDuration period: 2024-202
Biodegradability assessment of corn stover reinforced composite materials with different matrix
In this paper, the biodegradability of three SferiCorn™
biocomposites was investigated. Corn stover prepared through eco-friendly
washing and grinding to short fibers was used as reinforcement. Three different
biopolymers, corn starch, alginate and poly(3-hydroxybutyrate-co-3-
hydroxyvalerate) (PHBV), were used as matrices. The biodegradability of
prepared composites was investigated in a simulated soil burial test and the
samples were characterized in terms of weight loss and morphological changes. It
was shown that biodegradability can be tuned by biopolymers used as matrices.
Changes in the surface morphology after biodegradation of tested samples were
confirmed using scanning electron microscopy (SEM).Proceedings: 2nd International Symposium on Biotechnology, 14–15
March 202
SOIL MICROBIOME DIVERSITY IN MAIZE-WINTER WHEAT CROP ROTATION
The soil microbiome controls key functions in
agroecosystems determining soil fertility, crop
productivity, and stress tolerance. Crop rotation
is one of the oldest agricultural practices that has
a positive effect on soil quality and the control of
weeds, pests, and pathogens. New insights into
soil microbiome confirm the positive influence of
crop rotation on the diversity of the microbiome.
This study investigates the effects of different
crop rotations under conventional fertilization/
weed management practices on soil microbial
diversity and community structure in two of the
most commonly grown crops in Serbia. The study
investigated the bacterial population in samples
from long-term cultivation experiment of maize
continuous cropping (M-CC) and maize-winter
wheat rotation (M-WW) at two-time points
(December 2022 and May 2023). The results of
16S rDNA amplicon community profiling and
beta diversity analysis showed clear clustering
depending on season, cropping sequence, and
herbicide application. The results show that the
composition of the bacterial community in soil
is largely influenced by seasonal changes. When
comparing bacterial communities in the same
season (May), we observed a significantly higher
biodiversity in M-CC compared to M-WW soils,
suggesting that type of agricultural practice has
a significant impact on the composition of the
microbiome by influencing selection and survival
of specific microbial taxa. In addition, a significant
shift was observed between the bacterial
community composition in M-CC samples under
herbicide treatment and in control soils in December,
while the M-WW community was stable
under all conditions tested. Taxonomically, Actinobacteria
dominated the soil microbiome under
all conditions (53%), followed by Proteobacteria
(23%), Acidobacteria (15%), and Firmicutes (8%).
Despite fluctuations in relative abundance, some
interesting taxa, including Bacillus, Microlunatus,
and Blastococcus, dominated the soil microbiome
under all conditions. These data provide insights
into microbial dynamics, integrating the cultivation
methods with metagenomic approaches to
evaluate different cropping practices.Book of abstract: From biotechnology to human and planetary health XIII congress of microbiologists of Serbia with international participation Mikromed regio 5, ums series 24: 4th – 6th april 2024, Mona Plaza hotel, Belgrade, Serbi
Multiscale modeling uncovers 7q11.23 copy number variation–dependent changes in ribosomal biogenesis and neuronal maturation and excitability
Copy number variation (CNV) at 7q11.23 causes Williams-Beuren syndrome (WBS) and 7q microduplication syndrome (7Dup), neurodevelopmental disorders (NDDs) featuring intellectual disability accompanied by symmetrically opposite neurocognitive features. Although significant progress has been made in understanding the molecular mechanisms underlying 7q11.23-related pathophysiology, the propagation of CNV dosage across gene expression layers and their interplay remains elusive. Here we uncovered 7q11.23 dosage–dependent symmetrically opposite dynamics in neuronal differentiation and intrinsic excitability. By integrating transcriptomics, translatomics, and proteomics of patient-derived and isogenic induced neurons, we found that genes related to neuronal transmission follow 7q11.23 dosage and are transcriptionally controlled, while translational factors and ribosomal genes are posttranscriptionally buffered. Consistently, we found phosphorylated RPS6 (p-RPS6) downregulated in WBS and upregulated in 7Dup. Surprisingly, p-4EBP was changed in the opposite direction, reflecting dosage-specific changes in total 4EBP levels. This highlights different dosage-sensitive dyregulations of the mTOR pathway as well as distinct roles of p-RPS6 and p-4EBP during neurogenesis. Our work demonstrates the importance of multiscale disease modeling across molecular and functional layers, uncovers the pathophysiological relevance of ribosomal biogenesis in a paradigmatic pair of NDDs, and uncouples the roles of p-RPS6 and p-4EBP as mechanistically actionable relays in NDDs
miRNA-mediated inhibition of an actomyosin network in hippocampal pyramidal neurons restricts sociability in adult male mice
Social deficits are frequently observed in patients suffering from neurodevelopmental disorders, but the molecular mechanisms regulating sociability are still poorly understood. We recently reported that the loss of the microRNA (miRNA) cluster miR-379-410 leads to hypersocial behavior and anxiety in mice. Here, we show that ablating miR-379-410 in excitatory neurons of the postnatal mouse hippocampus recapitulates hypersociability, but not anxiety. At the cellular level, miR-379-410 loss in excitatory neurons leads to larger dendritic spines, increased excitatory synaptic transmission, and upregulation of an actomyosin gene network. Re-expression of three cluster miRNAs, as well as pharmacological inhibition of the actomyosin activator ROCK, is sufficient to reinstate normal sociability in miR-379-410 knockout mice. Several actomyosin genes and miR-379-410 family members are reciprocally dysregulated in isogenic human induced pluripotent stem cell (iPSC)-derived neurons harboring a deletion present in patients with Williams-Beuren syndrome, characterized by hypersocial behavior. Together, our results show an miRNA-actomyosin pathway involved in social behavior regulation
An Overview of 22q11.2 Diagnostic and Research Facilities in the Countries of The Western Balkan Region
Background: 22q11.2 deletion syndrome is the most common microdeletion disorder in humans, with the incidence of
approximately 1 in 2000 newborns. The Balkan region is characterized by many social and language interconnections,
intense people and services’ flow, but also diversity of health systems. The aim of the study was to analyze current state of
diagnostic and research programs in the Balkan region. Methods: A survey using 6-item-questionnaire was conducted
among clinical/medical geneticists of university clinical centers in Bosnia and
Herzegovina, Montenegro, Croatia and Serbia, and Macedonian Academy of Sciences and Arts in North Macedonia.
Results: The study showed that all countries involved in the survey provide diagnostic testing for 22q11.2 CNVs either in
domestic laboratories or by sending samples abroad. The survey’s results range from not having domestic 22q11.2
diagnostic or research programs in Montenegro to having several domestic diagnostic centers in Serbia and Croatia.
Regarding research activities, domestic and international research programs dedicated specifically to investigation of the
22q11.2 chromosomal region exist onlyBook of abstract: Praia D’El Rey Golf and Beach Resort Óbidos, Portugal | July 16 - July 18, 202