Biology subjects

Amini, S.

Publications and source records attributed to Amini, S..

18 recordsLinked to original sources

bioRxiv2026

Pufferfish inflation: drivers of axial and hoop skin strain and regional variation across the body

Pufferfish skin undergoes large multi-axial extensions during defensive inflation behaviour, as water is pumped into the stomach and the fish increases its body volume threefold. This remarkable capacity for deformation thus raises questions on how skin extension is spatially distributed across the body, and how skin extension relates to changes in body volume and stomach pressure. However, directly measuring skin extension remains experimentally challenging, particularly when attempting to preserve the bodys complex 3D geometry and natural multiaxial strain during ex vivo testing. We used biplanar x-ray videography to measure skin strain (fluoromicrometry) and body volume (dynamic digital endocast) simultaneously with stomach pressure recordings during natural and artificial inflations in porcupinefish ( Diodon holocanthus ). We found no significant difference in maximum body volumes (2.66 {+/-} 0.65 times their initial body volume), body dimensions (e.g., dorsoventral height 87.31 {+/-} 0.23 mm), peak pressures (2.45 {+/-} 1.10 kPa), and skin extension at maximum inflation between natural and artificial inflation conditions. In all inflations, volume increased steadily while stomach pressure only increased during the last 25-50% of inflation. Skin extension varied biaxially, with mean strains reaching up to 102% in the axial direction and 146% in the hoop direction as the fish became nearly spherical. The greatest skin extensions occurred most dorsocranially (axial) and ventrolaterally (hoop). Strains in the hoop direction were only significantly different between body regions (defined as dorsal, lateral and ventral), with the greatest hoop strains occurring in the ventral body region. Our findings may provide insight into existing hypotheses regarding the relationship between volume, pressure, and skin structure and behaviour, while also providing direct in vivo measurements to inform biomimetic design.

zoology↗

bioRxiv2026

Crystallization of magnesium calcite otoconia in the inner ear of the developing quail

Otolith organs are specialized structures of the vertebrate inner ear that provide the inertial mass required for maintaining equilibrium. Mammals possess two otolithic organs, the utricle and the saccule, whereas birds and other non-mammalian vertebrates also retain a third one, the lagena, whose development remains poorly understood and whose function is still debated. In birds, the lagena contains thousands of calcium carbonate biomineral particles, termed otoconia. Here, we reconstruct the developmental crystallization of lagena otoconia in the Japanese quail (Coturnix japonica) throughout embryogenesis. We combine multiscale imaging with structural, compositional, and crystallographic analyses across length scales. We show that lagena mineralization precedes cranial bone formation and proceeds predominantly through the growth of existing otoconia rather than continued nucleation. Otoconia develop through progressive particle growth, alignment, and fusion within a pre-existing organic compartment while maintaining a persistent central core, ultimately forming magnesium calcite biominerals. This maturation is accompanied by progressive nanoscale densification, transforming early mineral deposits into mature hierarchical crystals. This work establishes a developmental model of avian otoconia formation and provides new insights into how hierarchical calcium carbonate crystals are assembled during vertebrate development. Statement of significanceOtoliths are the only calcite based biomineral in our body that has a physiological function, yet their developmental assembly remain incompletely understood. While the utricle and saccule have been extensively investigated across vertebrates, the lagena, a third otolithic organ lost during mammalian evolution, has received comparatively little attention. Here, we combine multiscale imaging and materials characterization to reconstruct the developmental crystallization of lagena otoconia in the Japanese quail. We establish how hierarchical magnesium calcite biominerals emerge through coordinated mineral growth, structural maturation, and crystallization, providing a developmental framework for avian otoconia formation and new insights into the assembly of vertebrate calcium carbonate crystals.

developmental biology↗

bioRxiv2026

Affinity Fine-Tuning of Boltz-2: An Open Framework for Protein-Ligand Potency Prediction in Drug Discovery

Boltz-2 has enabled accurate binding affinity prediction by leveraging co-folded protein-ligand structures, but the absence of a public training recipe has limited its use in active drug discovery projects, where new experimental measurements and congeneric ligand series continually arrive during lead optimization. We present an open framework for affinity fine-tuning of Boltz-2, showing that adapting only the affinity prediction components with project-specific experimental data can make the model substantially more useful for lead optimization. We evaluate the approach in two internal studies: a multi-target retrospective benchmark against physics-based and machine learning baselines, and a large single-target study with up to 1,700 ligands. In both settings, fine-tuned Boltz-2 improves correlation over the off-the-shelf model, and in some cases reaches performance competitive with free energy perturbation (FEP) methods. By releasing this framework, we aim to enable the community to adapt Boltz-2 to the specific targets and data of their own drug discovery campaigns. The code is available at: https://github.com/molecularinformatics/Boltz2_affinity

molecular biology↗

bioRxiv2026

Mitochondria-insulin granule crosstalk controls the early stages of granule maturation

Insulin secretion from pancreatic {beta}-cells is a tightly controlled process where hormone synthesis, granule formation and release are regulated in order to maintain whole body glucose homeostasis. Failure to produce or release insulin results in hyperglycemia that may develop into diabetes. Insulin-containing granules exist in different pools that have different propensity for release, yet what determined the fate of a granule after initial formation is not clear. In this study we aimed to identify key steps in the early life of an insulin granule that directs it towards release. Using two different methods for time-dependent labeling, we found that insulin granules shortly after budding from the trans-Golgi network associate with mitochondria. This organelle interaction involves the voltage-dependent anion channel (VDAC) and the vesicular nucleotide transporter (VNUT). Reduced VNUT expression prevented the recruitment of VDAC to insulin granules and redirected granules towards autophagy-dependent lysosomal degradation, resulting in reduced insulin content and impaired insulin secretion. These results show the requirement of granule-mitochondria crosstalk for normal progression through the early stages of the secretory pathway.

cell biology↗

bioRxiv2026

E. coli extracellular matrix: a tunable composite with hierarchical structure

Escherichia coli (E. coli) biofilms consist of bacteria, an extracellular matrix (ECM) mainly made of curli amyloid fibers, phosphoethanolamine-modified cellulose (pEtN-cellulose), and water. While curli amyloid fibers contribute to biofilm rigidity, pEtN-cellulose contributes to their cohesion. This work explores the interplay between these fibers, and how their interaction influence biofilm structure and mechanical properties. We performed a multiscale analysis on E. coli biofilms grown using strains producing curli and pEtN-cellulose, and only curli and only pEtN-cellulose in co-seeded ratios. Micro-indentation experiments, confocal microscopy, and cryo-FIBSEM 3D imaging revealed a composite-like behavior of the biofilm, where its mechanical properties depend on ECM composition and organization. Spectroscopic analysis of the extracted fibers showed that their biophysical properties are influenced by their pEtN-cellulose to curli ratio and assembly. We propose that pEtN-cellulose swelling is contrained by its interactions with rigid curli fibers. The reference E. coli strain maximizes this effect by assembling a curli/pEtN-cellulose hybrid material at the sub-micron scale, where its composition, interactions, and architecture can explain biofilm emergent properties. This knowledge on microbial ECM assembly opens new avenues for engineering living materials, especially for the use of bacterial biofilms as a source of bio-sourced materials.

biophysics↗

bioRxiv2025

Cement lines are stiffer and harder than bone but exhibit different mineral-mechanics relationships due to thicker and shorter mineral particles

The remarkable mechanical performance of bone arises from its complex hierarchical structure and from the presence of numerous internal interfaces joining the different components. Formed during bone remodeling, the cement line (CL) is a thin interface surrounding osteons. Although often neglected due to its small size, the CL has been suggested to play an important role in bone fracture toughness. However, there is an ongoing debate about its specific structure and mechanical behavior. Here, we investigate the composition-mechanics relationship at the CL and surrounding bone in human osteons using multiple methods in a correlative manner. We found that the CL is stiffer and harder than adjacent osteonal tissue. However, the CL requires more mineral than bone to attain the same stiffness and hardness. Analyzing the nanoscale properties of the mineral, we found thicker but shorter particles at the CL. Using a mechanical model, we interpreted the lower aspect ratio of the mineral particles as a less effective way to reinforce the collagen matrix. Casting our findings into a computational model, we questioned the possible protective role of the CL, which is not a soft interface as traditionally believed.

bioengineering↗

bioRxiv2025

The Stmn1-lineage contributes to acinar regeneration but not to neoplasia upon oncogenic Kras expression

BACKGROUND & AIMSThe exocrine pancreas has a limited regenerative capacity, but to what extent all acinar cells are involved in this process is unclear. Nevertheless, the heterogenous nature of acinar cells suggests that cells exhibiting higher plasticity might play a more prominent role in acinar regeneration. In that regard, Stmn1-expressing acinar cells have been identified as potential facultative progenitor-like cells in the adult pancreas. Here, we studied Stmn1-progeny under physiological conditions, during regeneration, and in the context of KrasG12D expression. METHODSWe followed the fate of Stmn1-progenies both under baseline conditions, following caerulein-induced acute or chronic pancreatitis, pancreatic duct ligation, and in the context of KrasG12D expression. RESULTSThe Stmn1-lineage contributes to baseline acinar cell turnover under physiological conditions. Furthermore, these cells rapidly proliferate and repopulate the acinar compartment in response to acute injury in an ADM-independent manner. Moreover, acinar regeneration during chronic pancreatitis progression is in conjunction with a decline in the proliferative capacity of the Stmn1-lineage. Interestingly, newly generated acinar cells display increased susceptibility to additional injury during recurrent acute pancreatitis (RAP). Finally, given their inability to form ADMs, the Stmn1-lineage fails to form PanINs upon oncogenic Kras expression. CONCLUSIONSOur findings establish the Stmn1-lineage as a pivotal subpopulation for acinar regeneration. The ability of these cells to restore acinar tissue in an ADM-independent manner distinguishes them as a critical regenerative population. This study presents a new paradigm for acinar regeneration and repair in the context of pancreatitis and neoplasia.

cell biology↗

bioRxiv2025

Mechanical comparison of Escherichia coli biofilms with altered matrix composition: a study combining shear-rheology and microindentation

The mechanical properties of bacterial biofilms depend on the composition and micro-structure of their extracellular matrix (ECM), which constitutes a network of extracellular proteins and polysaccharide fibers. In particular, E. coli macrocolony biofilms were suggested to present tissue-like elasticity due to a dense fiber network consisting of amyloid curli and phosphoethanolamine-modified cellulose (pEtN-cellulose). To understand the contribution of these two main ECM components to the emergent mechanical properties of E. coli biofilms, we performed shear-rheology and microindentation experiments on biofilms grown from E. coli strains that produce different ECM. We measured that biofilms containing curli fibers are stiffer in compression than curli-deficient biofilms. We further quantitatively demonstrate the crucial contribution of pEtN-cellulose, and especially of the pEtN modification, to the stiffness and structural stability of biofilms when associated with curli fibers. To compare the differences observed between the two methods, we also investigated how the structure and mechanical properties of biofilms with different ECM compositions are affected by the sample preparation method used for shear-rheology. We found that biofilm homogenization, used prior to shear-rheology, destroys the macroscale structure of the biofilm while the microscopic ECM architecture may remain intact. The resulting changes in biofilm mechanical properties highlight the respective advantages and limitations of the two complementary mechanical characterization techniques in the context of biofilm research. As such, our work does not only describe the role of the ECM on the mechanical properties of E. coli biofilms. It also informs the biofilm community on considering sample preparation when interpreting mechanical data of biofilm-based materials.

biophysics↗

bioRxiv2024

Tabula Glycine: The whole-soybean single-cell resolution transcriptome atlas

Soybean (Glycine max) is an essential source of protein and oil with high nutritional value for human and animal consumption. To enhance our understanding of soybean biology, it is essential to have accurate information regarding the expression of each of its 55,897 protein-coding genes. Here, we present "Tabula Glycine", the soybean single-cell resolution transcriptome atlas. This atlas is composed of single-nucleus RNA-sequencing data of nearly 120,000 nuclei isolated from 10 different Glycine max organs and morphological structures comprising the entire soybean plant. These nuclei are grouped into 157 different clusters based on their transcriptomic profiles. Among genes, the pattern of activity of transcription factor genes is sufficient to define most cell types and their organ/morphological structure of origin, suggesting that transcription factors are key determinants of cell identity and function. This unprecedented level of resolution makes the Tabula Glycine a unique resource for the plant and soybean communities.

plant biology↗

bioRxiv2024

3D patterns in alginate hydrogel degradation spatially guide YAP nuclear translocation and hMSC osteogenic differentiation

Tissue engineering involves assembling cells and mimicking the complex anisotropic architecture of biological tissues to perform specific functions. This study explores the impact of patterned hydrogels with anisotropic degradation compared to single-phase materials on the potential of enhancing cell spreading, collective alignment, mechanotransduction and osteogenic differentiation of encapsulated human mesenchymal stromal cells (hMSCs). Spatial patterns of degradable (Deg) and non-degradable (noDeg) subregions are formed by photolithography: UV-triggered thiol-ene crosslinking with matrix metalloprotease (MMP) sensitive peptides form Deg phases, while non-UV exposed regions result in Diels-Alder spontaneous click crosslinking and noDeg phases. 3D patterns in hydrogel degradation enhance hMSC spreading and allow collective cell alignment in Deg areas, while cells remain rounded with no alignment in noDeg regions. In addition, we observe a boosted osteogenic differentiation when compared to single-phase materials, as mid osteogenic markers (osteocalcin) are expressed at day 14 in anisotropic gels, whereas in single-phase only early osteogenic markers are found (osterix). Mechanosensing pathways were evaluated using the expression and localization of YAP. Deg sections in patterned materials have an enhanced nuclear translocation and higher YAP expression compared to single-phase Deg materials and noDeg sections. This effect is lost and no patterns in YAP expression and localization emerge when using an MMP-scramble peptide or no-RGD materials. These findings demonstrate that 3D patterns in alginate hydrogel degradation guide hMSC spreading, collective alignment, enhance YAP nuclear translocation and osteogenic differentiation. Mimicking tissue anisotropy in 3D patterned hydrogels could have broad applications in biofabrication and tissue engineering. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/588803v3_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@f7aa3aorg.highwire.dtl.DTLVardef@1c8d2a4org.highwire.dtl.DTLVardef@17d2371org.highwire.dtl.DTLVardef@a1d6a2_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG

bioengineering↗

bioRxiv2023

Empowering human-like walking with a bio-inspired gait controller for an under-actuated torque- driven human model

Human gait simulation plays a crucial role in providing insights into various aspects of locomotion, such as diagnosing injuries and impairments, assessing abnormal gait patterns, and developing assistive and rehabilitation technologies. To achieve more realistic results in gait simulation, it is necessary to utilize a comprehensive model that closely replicates the kinematics and kinetics of the human gait pattern. OpenSim software provides anthropomorphic and anatomically accurate human skeletal structures that enable users to create personalized models for individuals to accurately replicate real human behavior. However, torque-driven models face challenges in balancing unactuated degrees of freedom during forward dynamic simulations. Adopting a bio-inspired strategy that ensures an individuals balance with a minimized energy expenditure, this paper proposes a gait controller for a torque-deriven OpenSim model to achieve a stable walking. The proposed controller takes a model-based approach to calculate a "Balance Equivalent Control Torque" and uses the concept of the hip-ankle strategy to distribute this balance torque to the lower-limb joints. To optimize the controller gains and the "Balance Distribution Coefficients", an interface is stablished between MATLAB and OpenSim that is capable of conducting controllable forward dynamic simulations. The simulation results demonstrate that the torque-driven model can walk naturally with joint torques suitably matching experimental data. The robustness of the bio-inspired gait controller is also assessed by applying a range of external forces on the upper body to disturb the model. The robustness analysis demonstrates the quick and effective balance recovery mechanism of the proposed bio-inspired controller.

bioengineering↗

bioRxiv2023

Hydrogels with stiffness-degradation spatial patterns control anisotropic 3D cell response

In nature, tissues are patterned, but most biomaterials used in human applications are not. Patterned biomaterials offer the opportunity to mimic spatially segregating biophysical and biochemical properties found in nature. Engineering such properties allows to study cell-matrix interactions in anisotropic matrices in great detail. Here, we developed alginate-based hydrogels with patterns in stiffness and degradation, composed of distinct areas of soft non-degradable (Soft-NoDeg) and stiff degradable (Stiff-Deg) material properties. The hydrogels exhibit emerging patterns in stiffness and degradability over time, taking advantage of dual Diels-Alder covalent crosslinking and UV-mediated peptide crosslinking. The materials were mechanically characterized using rheology for single-phase and surface micro-indentation for patterned materials. 3D encapsulated mouse embryonic fibroblasts (MEFs) allowed to characterize the anisotropic cell-matrix interaction in terms of cell morphology by employing a novel image-based quantification tool. Live/dead staining showed no differences in cell viability but distinct patterns in proliferation, with higher cell number in Stiff-Deg materials at day 14. Patterns of projected cell area became visible already at day 1, with larger values in Soft-NoDeg materials. This was inverted at day 14, when larger projected cell areas were identified in Stiff-Deg. This shift was accompanied by a significant decrease in cell circularity in Stiff-Deg. The control of anisotropic cell morphology by the material patterns was also confirmed by a significant increase in filopodia number and length in Stiff-Deg materials. The novel image-based quantification tool was useful to spatially visualize and quantify the anisotropic cell response in 3D hydrogels with stiffness-degradation spatial patterns. Our results show that patterning of stiffness and degradability allows to control cell anisotropic response in 3D and can be quantified by image-based strategies. This allows a deeper understanding of cell-matrix interactions in a multicomponent material.

bioengineering↗

bioRxiv2022

Calcitic prisms of the giant seashell Pinna nobilis form light guide arrays

The shells of the Pinnidae family are based on a double layer of single-crystal-like calcitic prisms and inner aragonitic nacre, a structure known for its outstanding mechanical performance. However, on the posterior side, shells are missing the nacreous layer, which raises the question of whether there could be any functional role in giving up this mechanical performance. Here, we demonstrate that the prismatic part of the Pinna nobilis shell exhibits unusual optical properties, whereby each prism acts as an individual optical fiber guiding the ambient light to the inner shell cavity by total internal reflection. This pixelated light channeling enhances both spatial resolution and contrast while reducing angular blurring, an apt combination for acute tracking of a moving object. Our findings may offer insights into the evolutionary aspects of light-sensing and imaging by biological materials and introduce a conceptual framework for the development of bio-inspired multifunctional ceramics and architectured light-tracking materials.

biophysics↗

bioRxiv2020

Transcriptional regulation of ZIP genes is independent of local zinc status in Brachypodium shoots upon zinc deficiency and resupply

The biological processes underlying zinc homeostasis are targets for genetic improvement of crops to counter human malnutrition. Detailed phenotyping, ionomic, RNA-Seq analyses and flux measurements with 67Zn isotope revealed whole plant molecular events underlying zinc homeostasis upon varying zinc supply and during zinc resupply to starved Brachypodium distachyon (Brachypodium) plants. Although both zinc deficiency and excess hindered Brachypodium growth, accumulation of biomass and micronutrients into roots and shoots differed depending on zinc supply. The zinc resupply dynamics involved 1893 zinc-responsive genes. Multiple ZIP transporter genes and dozens of other genes were rapidly and transiently down-regulated in early stages of zinc resupply, suggesting a transient zinc shock, sensed locally in roots. Notably genes with identical regulation were observed in shoots without zinc accumulation, pointing to root-to-shoot signals mediating whole plant responses to zinc resupply. Molecular events uncovered in the grass model Brachypodium are useful for the improvement of staple monocots.

plant biology↗

bioRxiv2020

A comprehensive map of genetic interactions in childhood cancer reveals multiple underlying biological mechanisms

Childhood cancer is a major cause of child death in developed countries. Genetic interactions between mutated genes play an important role in cancer development. They can be detected by searching for pairs of mutated genes that co-occur more (or less) often than expected. Co-occurrence suggests a cooperative role in cancer development, while mutual exclusivity points to synthetic lethality, a phenomenon of interest in cancer treatment research. Little is known about genetic interactions in childhood cancer. We apply a statistical pipeline to detect genetic interactions in a combined dataset comprising over 2,500 tumors from 23 cancer types. The resulting genetic interaction map of childhood cancers comprises 15 co-occurring and 27 mutually exclusive candidates. The biological mechanisms underlying most candidates are either tumor subtype, pathway epistasis or cooperation while synthetic lethality plays a much smaller role. Thus, other explanations beyond synthetic lethality should be considered when interpreting results of genetic interaction tests.

cancer biology↗

bioRxiv2019

Resolution of the proteome, transcript and ionome dynamics upon Zn re-supply in Zn-deficient Arabidopsis

O_LIRegulation of plant Zn acquisition is poorly understood, while Zn deficiency affects over 2 billion people worldwide. We therefore dissected the dynamic response to changes in Zn supply in Arabidopsis. C_LIO_LIHydroponically-grown Zn starved plants were re-supplied with Zn. Subsequent time-resolved sampling strategy allowed concomitant quantification of the dynamics of Zn uptake, microsomal and soluble proteins, and specific transcripts, in space (roots and shoots) and time. C_LIO_LIZn accumulates in roots within 10min, but 8h are needed before shoot Zn increases. By 8h, root Zn concentration was ~60% of non-starved plants. Overexpressed root Zn transporters further peaked in 10-30min post re-supply, before reaching a minimum in 120min and 200 ppm Zn. Zn-responding signaling/regulatory molecules include receptor and MAP kinases, calcium signaling proteins, phosphoinositides, G-proteins, COP9 signalosome members, as well as multiple transcription factors. C_LIO_LIZn acquisition is a highly controlled dynamic process. Our study identifies novel players in Zn homeostasis and points to cross-talk with other nutrients. It paves the way for directed investigation of so far omitted candidates which dynamically respond to sudden changes in Zn supply but are expressed at similar levels at steady-state Zn deficiency and sufficiency. C_LI

plant biology↗

bioRxiv2019

Emergence of multidrug-resistant Mycobacterium simiae: An in vitro study from a regional tuberculosis reference laboratory in Iran

IntroductionMycobacterium simiae is an emerging pathogen in Iran and little is known about drug susceptibility patterns of this pathogen. Materials and methodsTwenty five clinical isolates of M. simiae from 80 patients with confirmed NTM pulmonary disease were included in this study. For drug susceptibility testing (DST), proportional and broth microdilution methods were used according to the clinical and laboratory standards institute (CLSI) guideline. ResultsAll clinical isolates of M. simiae were resistant to isoniazid, rifampicin, ethambutol, streptomycin, amikacin, kanamycin, ciprofloxacin and clarithromycin. They also were highly resistant to ofloxacin (80%). Susceptibility to ofloxacin was only noted in the 5 isolates. ConclusionsClinical isolates of M. simiae were multidrug resistant, and had different drug susceptibility patterns than previously published studies. DST results can assist in selecting more appropriate treatment regimens. Newer drugs with proven clinical efficacy correlating with in vitro susceptibility should be substituted with first- and second line anti-TB drug testing.

microbiology↗

bioRxiv2018

The ability of transcription factors to differentially regulate gene expression is a crucial component of the mechanism underlying inversion, a frequently observed genetic interaction pattern

Genetic interactions, a phenomenon whereby combinations of mutations lead to unexpected effects, reflect how cellular processes are wired and play an important role in complex genetic diseases. Understanding the molecular basis of genetic interactions is crucial for deciphering pathway organization as well as understanding the relationship between genetic variation and disease. Several putative molecular mechanisms have been linked to different genetic interaction types. However, differences in genetic interaction patterns and their underlying mechanisms have not yet been compared systematically between different functional gene classes. Here, differences in the occurrence and types of genetic interactions are compared for two classes, gene-specific transcription factors (GSTFs) and signaling genes (kinases and phosphatases). Genome-wide gene expression data for 63 single and double deletion mutants in bakers yeast reveals that the two most common genetic interaction patterns are buffering and inversion. Buffering is typically associated with redundancy and is well understood. In inversion, genes show opposite behavior in the double mutant compared to the corresponding single mutants. The underlying mechanism is poorly understood. Although both classes show buffering and inversion patterns, the prevalence of inversion is much stronger in GSTFs. To decipher potential mechanisms, a Petri Net modeling approach was employed, where genes are represented as nodes and relationships between genes as edges. This allowed over 9 million possible three and four node models to be exhaustively enumerated. The models show that a quantitative difference in interaction strength is a strict requirement for obtaining inversion. In addition, this difference is frequently accompanied with a second gene that shows buffering. Taken together, these results provide a mechanistic explanation for inversion. Furthermore, the ability of transcription factors to differentially regulate expression of their targets provides a likely explanation why inversion is more prevalent for GSTFs compared to kinases and phosphatases.\n\nAuthor SummaryThe relationship between genotype and phenotype is one of the major challenges in biology. While many previous studies have identified genes involved in complex genetic diseases, there is still a gap between genotype and phenotype. One of the difficulties in filling this gap has been attributed to genetic interactions. Large-scale studies have revealed that genetic interactions are widespread in model organisms such as bakers yeast. Several molecular mechanisms have been proposed for different genetic interaction types. However, differences in occurrence and underlying molecular mechanism of genetic interactions have not yet been compared between gene classes of different function. Here, we compared genetic interaction patterns identified using gene expression profiling for two classes of genes: gene specific transcription factors and signaling related genes. We modelled all possible molecular networks to unravel putative molecular differences underlying different genetic interaction patterns. Our study proposes a new mechanistic explanation for a certain genetic interaction pattern that is more strongly associated with transcription factors compared to signaling related genes. Overall, our findings and the computational methodologies implemented here can be valuable for understanding the molecular mechanisms underlying genetic interactions.

genetics↗