Spatiotemporal organization of protein interactions in cell signaling is a fundamental process th... more Spatiotemporal organization of protein interactions in cell signaling is a fundamental process that drives cellular functions. Given differential protein expression across tissues and developmental stages, the architecture and dynamics of signaling interaction proteomes is, likely, highly context dependent. However, current interaction information has been almost exclusively obtained from transformed cells. In this study, we applied an advanced and robust workflow combining mouse genetics and affinity purification (AP)-SWATH mass spectrometry to profile the dynamics of 53 high-confidence protein interactions in primary T cells, using the scaffold protein GRB2 as a model. The workflow also provided a sufficient level of robustness to pinpoint differential interaction dynamics between two similar, but functionally distinct, primary T cell populations. Altogether, we demonstrated that precise and reproducible quantitative measurements of protein interaction dynamics can be achieved in ...
Cyclic adenosine monophosphate (cAMP) and Ca(2+) levels may oscillate in harmony within excitable... more Cyclic adenosine monophosphate (cAMP) and Ca(2+) levels may oscillate in harmony within excitable cells; a mathematical oscillation loop model, the Cooper model, of these oscillations was developed two decades ago. However, in that model all adenylyl cyclase (AC) isoforms were assumed to be inhibited by Ca(2+), and it is now known that the heart expresses multiple AC isoforms, among which the type 5/6 isoforms are Ca(2+)-inhibitable whereas the other five (AC2, 3, 4, 7, and 9) are not. We used a computational systems biology approach with CellDesigner simulation software to develop a comprehensive graphical map and oscillation loop model for cAMP and Ca(2+). This model indicated that Ca(2+)-mediated inhibition of AC is essential to create oscillations of Ca(2+) and cAMP, and the oscillations were not altered by incorporation of phosphodiesterase-mediated cAMP hydrolysis or PKA-mediated inhibition of AC into the model. More importantly, they were created but faded out immediately in ...
Increased availability of bioinformatics resources is creating opportunities for the application ... more Increased availability of bioinformatics resources is creating opportunities for the application of network pharmacology to predict drug effects and toxicity resulting from multi-target interactions. Here we present a high-precision computational prediction approach that combines two elaborately built machine learning systems and multiple molecular docking tools to assess binding potentials of a test compound against proteins involved in a complex molecular network. One of the two machine learning systems is a re-scoring function to evaluate binding modes generated by docking tools. The second is a binding mode selection function to identify the most predictive binding mode. Results from a series of benchmark validations and a case study show that this approach surpasses the prediction reliability of other techniques and that it also identifies either primary or off-targets of kinase inhibitors. Integrating this approach with molecular network maps makes it possible to address drug ...
Specialized languages used for describing computational models in the field of systems biology an... more Specialized languages used for describing computational models in the field of systems biology and physiology, such as Systems Biology Markup Language (SBML), CellML, and Physiological Hierarchy Markup Language (PHML), have been devised to enhance effective model reuse and sharing among researchers for developing large, multilevel models. Each language has its own specialty. By combining two of these languages, i. e. SBML for illustrating subcellular phenomena and PHML for expressing supracellular dynamics, a novel technology has been developed to describe models of multilevel biophysiological systems. For practical use of the aforementioned languages, consolidated software applications providing intuitive graphical user interfaces are necessary. Starting from 2011, a versatile platform called PhysioDesigner has been developed for multilevel modeling of physiological systems based on PHML. In this article, we focus on the newly developed distinguishing features of PhysioDesigner and PHML for the development of multilevel biophysiological models using SBML-PHML hybridization.
Elucidating gene regulatory network (GRN) from large scale experimental data remains a central ch... more Elucidating gene regulatory network (GRN) from large scale experimental data remains a central challenge in systems biology. Recently, numerous techniques, particularly consensus driven approaches combining different algorithms, have become a potentially promising strategy to infer accurate GRNs. Here, we develop a novel consensus inference algorithm, TopkNet that can integrate multiple algorithms to infer GRNs. Comprehensive performance benchmarking on a cloud computing framework demonstrated that (i) a simple strategy to combine many algorithms does not always lead to performance improvement compared to the cost of consensus and (ii) TopkNet integrating only high-performance algorithms provide significant performance improvement compared to the best individual algorithms and community prediction. These results suggest that a priori determination of high-performance algorithms is a key to reconstruct an unknown regulatory network. Similarity among gene-expression datasets can be useful to determine potential optimal algorithms for reconstruction of unknown regulatory networks, i.e., if expression-data associated with known regulatory network is similar to that with unknown regulatory network, optimal algorithms determined for the known regulatory network can be repurposed to infer the unknown regulatory network. Based on this observation, we developed a quantitative measure of similarity among gene-expression datasets and demonstrated that, if similarity between the two expression datasets is high, TopkNet integrating algorithms that are optimal for known dataset perform well on the unknown dataset. The consensus framework, TopkNet, together with the similarity measure proposed in this study provides a powerful strategy towards harnessing the wisdom of the crowds in reconstruction of unknown regulatory networks.
The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proliferation.... more The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proliferation. mTOR signaling is frequently dysregulated in oncogenic cells, and thus an attractive target for anticancer therapy. Using CellDesigner, a modeling support software for graphical notation, we present herein a comprehensive map of the mTOR signaling network, which includes 964 species connected by 777 reactions. The map complies with both the systems biology markup language (SBML) and graphical notation (SBGN) for computational analysis and graphical representation, respectively. As captured in the mTOR map, we review and discuss our current understanding of the mTOR signaling network and highlight the impact of mTOR feedback and crosstalk regulations on drug‐based cancer therapy. This map is available on the Payao platform, a Web 2.0 based community‐wide interactive process for creating more accurate and information‐rich databases. Thus, this comprehensive map of the mTOR network will se...
Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a co... more Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is rapidly increasing and needs to be efficiently organized, so that the resulting data is available for exploration and analysis. Here we introduce a computationally tractable, comprehensive molecular interaction map of PD. This map integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation. We also present bioinformatics tools for the analysis, enrichment and annotation of the map, allowing the research community to open new avenues in PD research. The PD map is accessible at http://minerva.uni.lu/pd_map.
BackgroundInfluenza is a common infectious disease caused by influenza viruses. Annual epidemics ... more BackgroundInfluenza is a common infectious disease caused by influenza viruses. Annual epidemics cause severe illnesses, deaths, and economic loss around the world. To better defend against influenza viral infection, it is essential to understand its mechanisms and associated host responses. Many studies have been conducted to elucidate these mechanisms, however, the overall picture remains incompletely understood. A systematic understanding of influenza viral infection in host cells is needed to facilitate the identification of influential host response mechanisms and potential drug targets.DescriptionWe constructed a comprehensive map of the influenza A virus (‘IAV’) life cycle (‘FluMap’) by undertaking a literature-based, manual curation approach. Based on information obtained from publicly available pathway databases, updated with literature-based information and input from expert virologists and immunologists, FluMap is currently composed of 960 factors (i.e., proteins, mRNAs e...
Background: Interpreting in vivo sampled microarray data is often complicated by changes in the c... more Background: Interpreting in vivo sampled microarray data is often complicated by changes in the cell population demographics. To put gene expression into its proper biological context, it is necessary to distinguish differential gene transcription from artificial gene expression induced by changes in the cellular demographics. Results: CTen (cell type enrichment) is a web-based analytical tool which uses our highly expressed, cell specific (HECS) gene database to identify enriched cell types in heterogeneous microarray data. The web interface is designed for differential expression and gene clustering studies, and the enrichment results are presented as heatmaps or downloadable text files. Conclusions: In this work, we use an independent, cell-specific gene expression data set to assess CTen's performance in accurately identifying the appropriate cell type and provide insight into the suggested level of enrichment to optimally minimize the number of false discoveries. We show that CTen, when applied to microarray data developed from infected lung tissue, can correctly identify the cell signatures of key lymphocytes in a highly heterogeneous environment and compare its performance to another popular bioinformatics tool. Furthermore, we discuss the strong implications cell type enrichment has in the design of effective microarray workflow strategies and show that, by combining CTen with gene expression clustering, we may be able to determine the relative changes in the number of key cell types.
Background Alzheimer's disease (AD) is the most common cause of dementia among the elderly. To cl... more Background Alzheimer's disease (AD) is the most common cause of dementia among the elderly. To clarify pathogenesis of AD, thousands of reports have been accumulating. However, knowledge of signaling pathways in the field of AD has not been compiled as a database before.
Background The challenge today is to develop a modeling and simulation paradigm that integrates s... more Background The challenge today is to develop a modeling and simulation paradigm that integrates structural, molecular and genetic data for a quantitative understanding of physiology and behavior of biological processes at multiple scales. This modeling method requires techniques that maintain a reasonable accuracy of the biological process and also reduces the computational overhead.
Abstract Elvitegravir is a new-generation drug which acts as an integrase inhibitor of the HIV vi... more Abstract Elvitegravir is a new-generation drug which acts as an integrase inhibitor of the HIV virus. The potential inhibition has been tested from the clinical trial data. Here the work basically deals with the quantitative structure-activity relationship (QSAR) analysis by considering some of the physiochemical descriptors like molecular weight, logP, molar volume, and structural descriptors like Winers index, and molecular topological index of the drug analogs.
Abstract The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proli... more Abstract The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proliferation. mTOR signaling is frequently dysregulated in oncogenic cells, and thus an attractive target for anticancer therapy. Using CellDesigner, a modeling support software for graphical notation, we present herein a comprehensive map of the mTOR signaling network, which includes 964 species connected by 777 reactions.
Abstract In this study, we have examined the patterns of VOCs released from used Tedlar bags that... more Abstract In this study, we have examined the patterns of VOCs released from used Tedlar bags that were once used for the collection under strong source activities. In this way, we attempted to account for the possible bias associated with the repetitive use of Tedlar bags. To this end, we selected the bags that were never heated. All of these target bags were used in ambient temperature (typically at or below 30 C). These bags were also dealt carefully to avoid any mechanical abrasion.
22 S. Ghosh et al. significant role as most patients are in the lowest income bracket of the soci... more 22 S. Ghosh et al. significant role as most patients are in the lowest income bracket of the society. This implies new drugs have to be developed in an innovative manner that allows delivery of drugs at low cost. Drug discovery is in general an expensive and capital-intensive process. A new type of big science is emerging that involves knowledge integration of small sciences as well as coordinating community-based participation.
A 2-year experiment was conducted in the alluvial tract of West Bengal to study appropriate P and... more A 2-year experiment was conducted in the alluvial tract of West Bengal to study appropriate P and K management strategies in a jute-kharif (winter) rice-boro (summer) rice sequence under a lowland rice ecosystem. Compared to State recommended rates, the approach based on soil testing did lead to higher crop yields, net returns, and relative agronomic effectiveness.
Abstract With the completion of the human genome project and the complete genome sequencing of ot... more Abstract With the completion of the human genome project and the complete genome sequencing of other organisms, huge databases cataloguing the various molecular “parts” of complex biological systems, have been opened up to scientists. As huge volumes of high throughput experimental data become available, the focus is shifting from studying biological systems as static models of loosely linked molecular devices to understanding their ensemble dynamics.
While the problem of optimal cell-site partitioning has been primarily studied from the perspecti... more While the problem of optimal cell-site partitioning has been primarily studied from the perspective of scarce radio resources in the access network, recent field measurements have shown significant impact of paging load on the core signaling subsystem capacity. In this paper, we revisit the problem of optimal zone partitioning, identifying factors affecting partitioning cost at the core switch.
Abstract Background: A key physiological mechanism employed by multicellular organisms is apoptos... more Abstract Background: A key physiological mechanism employed by multicellular organisms is apoptosis, or programmed cell death. Apoptosis is triggered by the activation of caspases in response to both extracellular (extrinsic) and intracellular (intrinsic) signals. The extrinsic and intrinsic pathways are characterized by the formation of the death-inducing signaling complex (DISC) and the apoptosome, respectively; both the DISC and the apoptosome are oligomers with complex formation dynamics.
Spatiotemporal organization of protein interactions in cell signaling is a fundamental process th... more Spatiotemporal organization of protein interactions in cell signaling is a fundamental process that drives cellular functions. Given differential protein expression across tissues and developmental stages, the architecture and dynamics of signaling interaction proteomes is, likely, highly context dependent. However, current interaction information has been almost exclusively obtained from transformed cells. In this study, we applied an advanced and robust workflow combining mouse genetics and affinity purification (AP)-SWATH mass spectrometry to profile the dynamics of 53 high-confidence protein interactions in primary T cells, using the scaffold protein GRB2 as a model. The workflow also provided a sufficient level of robustness to pinpoint differential interaction dynamics between two similar, but functionally distinct, primary T cell populations. Altogether, we demonstrated that precise and reproducible quantitative measurements of protein interaction dynamics can be achieved in ...
Cyclic adenosine monophosphate (cAMP) and Ca(2+) levels may oscillate in harmony within excitable... more Cyclic adenosine monophosphate (cAMP) and Ca(2+) levels may oscillate in harmony within excitable cells; a mathematical oscillation loop model, the Cooper model, of these oscillations was developed two decades ago. However, in that model all adenylyl cyclase (AC) isoforms were assumed to be inhibited by Ca(2+), and it is now known that the heart expresses multiple AC isoforms, among which the type 5/6 isoforms are Ca(2+)-inhibitable whereas the other five (AC2, 3, 4, 7, and 9) are not. We used a computational systems biology approach with CellDesigner simulation software to develop a comprehensive graphical map and oscillation loop model for cAMP and Ca(2+). This model indicated that Ca(2+)-mediated inhibition of AC is essential to create oscillations of Ca(2+) and cAMP, and the oscillations were not altered by incorporation of phosphodiesterase-mediated cAMP hydrolysis or PKA-mediated inhibition of AC into the model. More importantly, they were created but faded out immediately in ...
Increased availability of bioinformatics resources is creating opportunities for the application ... more Increased availability of bioinformatics resources is creating opportunities for the application of network pharmacology to predict drug effects and toxicity resulting from multi-target interactions. Here we present a high-precision computational prediction approach that combines two elaborately built machine learning systems and multiple molecular docking tools to assess binding potentials of a test compound against proteins involved in a complex molecular network. One of the two machine learning systems is a re-scoring function to evaluate binding modes generated by docking tools. The second is a binding mode selection function to identify the most predictive binding mode. Results from a series of benchmark validations and a case study show that this approach surpasses the prediction reliability of other techniques and that it also identifies either primary or off-targets of kinase inhibitors. Integrating this approach with molecular network maps makes it possible to address drug ...
Specialized languages used for describing computational models in the field of systems biology an... more Specialized languages used for describing computational models in the field of systems biology and physiology, such as Systems Biology Markup Language (SBML), CellML, and Physiological Hierarchy Markup Language (PHML), have been devised to enhance effective model reuse and sharing among researchers for developing large, multilevel models. Each language has its own specialty. By combining two of these languages, i. e. SBML for illustrating subcellular phenomena and PHML for expressing supracellular dynamics, a novel technology has been developed to describe models of multilevel biophysiological systems. For practical use of the aforementioned languages, consolidated software applications providing intuitive graphical user interfaces are necessary. Starting from 2011, a versatile platform called PhysioDesigner has been developed for multilevel modeling of physiological systems based on PHML. In this article, we focus on the newly developed distinguishing features of PhysioDesigner and PHML for the development of multilevel biophysiological models using SBML-PHML hybridization.
Elucidating gene regulatory network (GRN) from large scale experimental data remains a central ch... more Elucidating gene regulatory network (GRN) from large scale experimental data remains a central challenge in systems biology. Recently, numerous techniques, particularly consensus driven approaches combining different algorithms, have become a potentially promising strategy to infer accurate GRNs. Here, we develop a novel consensus inference algorithm, TopkNet that can integrate multiple algorithms to infer GRNs. Comprehensive performance benchmarking on a cloud computing framework demonstrated that (i) a simple strategy to combine many algorithms does not always lead to performance improvement compared to the cost of consensus and (ii) TopkNet integrating only high-performance algorithms provide significant performance improvement compared to the best individual algorithms and community prediction. These results suggest that a priori determination of high-performance algorithms is a key to reconstruct an unknown regulatory network. Similarity among gene-expression datasets can be useful to determine potential optimal algorithms for reconstruction of unknown regulatory networks, i.e., if expression-data associated with known regulatory network is similar to that with unknown regulatory network, optimal algorithms determined for the known regulatory network can be repurposed to infer the unknown regulatory network. Based on this observation, we developed a quantitative measure of similarity among gene-expression datasets and demonstrated that, if similarity between the two expression datasets is high, TopkNet integrating algorithms that are optimal for known dataset perform well on the unknown dataset. The consensus framework, TopkNet, together with the similarity measure proposed in this study provides a powerful strategy towards harnessing the wisdom of the crowds in reconstruction of unknown regulatory networks.
The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proliferation.... more The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proliferation. mTOR signaling is frequently dysregulated in oncogenic cells, and thus an attractive target for anticancer therapy. Using CellDesigner, a modeling support software for graphical notation, we present herein a comprehensive map of the mTOR signaling network, which includes 964 species connected by 777 reactions. The map complies with both the systems biology markup language (SBML) and graphical notation (SBGN) for computational analysis and graphical representation, respectively. As captured in the mTOR map, we review and discuss our current understanding of the mTOR signaling network and highlight the impact of mTOR feedback and crosstalk regulations on drug‐based cancer therapy. This map is available on the Payao platform, a Web 2.0 based community‐wide interactive process for creating more accurate and information‐rich databases. Thus, this comprehensive map of the mTOR network will se...
Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a co... more Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is rapidly increasing and needs to be efficiently organized, so that the resulting data is available for exploration and analysis. Here we introduce a computationally tractable, comprehensive molecular interaction map of PD. This map integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation. We also present bioinformatics tools for the analysis, enrichment and annotation of the map, allowing the research community to open new avenues in PD research. The PD map is accessible at http://minerva.uni.lu/pd_map.
BackgroundInfluenza is a common infectious disease caused by influenza viruses. Annual epidemics ... more BackgroundInfluenza is a common infectious disease caused by influenza viruses. Annual epidemics cause severe illnesses, deaths, and economic loss around the world. To better defend against influenza viral infection, it is essential to understand its mechanisms and associated host responses. Many studies have been conducted to elucidate these mechanisms, however, the overall picture remains incompletely understood. A systematic understanding of influenza viral infection in host cells is needed to facilitate the identification of influential host response mechanisms and potential drug targets.DescriptionWe constructed a comprehensive map of the influenza A virus (‘IAV’) life cycle (‘FluMap’) by undertaking a literature-based, manual curation approach. Based on information obtained from publicly available pathway databases, updated with literature-based information and input from expert virologists and immunologists, FluMap is currently composed of 960 factors (i.e., proteins, mRNAs e...
Background: Interpreting in vivo sampled microarray data is often complicated by changes in the c... more Background: Interpreting in vivo sampled microarray data is often complicated by changes in the cell population demographics. To put gene expression into its proper biological context, it is necessary to distinguish differential gene transcription from artificial gene expression induced by changes in the cellular demographics. Results: CTen (cell type enrichment) is a web-based analytical tool which uses our highly expressed, cell specific (HECS) gene database to identify enriched cell types in heterogeneous microarray data. The web interface is designed for differential expression and gene clustering studies, and the enrichment results are presented as heatmaps or downloadable text files. Conclusions: In this work, we use an independent, cell-specific gene expression data set to assess CTen's performance in accurately identifying the appropriate cell type and provide insight into the suggested level of enrichment to optimally minimize the number of false discoveries. We show that CTen, when applied to microarray data developed from infected lung tissue, can correctly identify the cell signatures of key lymphocytes in a highly heterogeneous environment and compare its performance to another popular bioinformatics tool. Furthermore, we discuss the strong implications cell type enrichment has in the design of effective microarray workflow strategies and show that, by combining CTen with gene expression clustering, we may be able to determine the relative changes in the number of key cell types.
Background Alzheimer's disease (AD) is the most common cause of dementia among the elderly. To cl... more Background Alzheimer's disease (AD) is the most common cause of dementia among the elderly. To clarify pathogenesis of AD, thousands of reports have been accumulating. However, knowledge of signaling pathways in the field of AD has not been compiled as a database before.
Background The challenge today is to develop a modeling and simulation paradigm that integrates s... more Background The challenge today is to develop a modeling and simulation paradigm that integrates structural, molecular and genetic data for a quantitative understanding of physiology and behavior of biological processes at multiple scales. This modeling method requires techniques that maintain a reasonable accuracy of the biological process and also reduces the computational overhead.
Abstract Elvitegravir is a new-generation drug which acts as an integrase inhibitor of the HIV vi... more Abstract Elvitegravir is a new-generation drug which acts as an integrase inhibitor of the HIV virus. The potential inhibition has been tested from the clinical trial data. Here the work basically deals with the quantitative structure-activity relationship (QSAR) analysis by considering some of the physiochemical descriptors like molecular weight, logP, molar volume, and structural descriptors like Winers index, and molecular topological index of the drug analogs.
Abstract The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proli... more Abstract The mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proliferation. mTOR signaling is frequently dysregulated in oncogenic cells, and thus an attractive target for anticancer therapy. Using CellDesigner, a modeling support software for graphical notation, we present herein a comprehensive map of the mTOR signaling network, which includes 964 species connected by 777 reactions.
Abstract In this study, we have examined the patterns of VOCs released from used Tedlar bags that... more Abstract In this study, we have examined the patterns of VOCs released from used Tedlar bags that were once used for the collection under strong source activities. In this way, we attempted to account for the possible bias associated with the repetitive use of Tedlar bags. To this end, we selected the bags that were never heated. All of these target bags were used in ambient temperature (typically at or below 30 C). These bags were also dealt carefully to avoid any mechanical abrasion.
22 S. Ghosh et al. significant role as most patients are in the lowest income bracket of the soci... more 22 S. Ghosh et al. significant role as most patients are in the lowest income bracket of the society. This implies new drugs have to be developed in an innovative manner that allows delivery of drugs at low cost. Drug discovery is in general an expensive and capital-intensive process. A new type of big science is emerging that involves knowledge integration of small sciences as well as coordinating community-based participation.
A 2-year experiment was conducted in the alluvial tract of West Bengal to study appropriate P and... more A 2-year experiment was conducted in the alluvial tract of West Bengal to study appropriate P and K management strategies in a jute-kharif (winter) rice-boro (summer) rice sequence under a lowland rice ecosystem. Compared to State recommended rates, the approach based on soil testing did lead to higher crop yields, net returns, and relative agronomic effectiveness.
Abstract With the completion of the human genome project and the complete genome sequencing of ot... more Abstract With the completion of the human genome project and the complete genome sequencing of other organisms, huge databases cataloguing the various molecular “parts” of complex biological systems, have been opened up to scientists. As huge volumes of high throughput experimental data become available, the focus is shifting from studying biological systems as static models of loosely linked molecular devices to understanding their ensemble dynamics.
While the problem of optimal cell-site partitioning has been primarily studied from the perspecti... more While the problem of optimal cell-site partitioning has been primarily studied from the perspective of scarce radio resources in the access network, recent field measurements have shown significant impact of paging load on the core signaling subsystem capacity. In this paper, we revisit the problem of optimal zone partitioning, identifying factors affecting partitioning cost at the core switch.
Abstract Background: A key physiological mechanism employed by multicellular organisms is apoptos... more Abstract Background: A key physiological mechanism employed by multicellular organisms is apoptosis, or programmed cell death. Apoptosis is triggered by the activation of caspases in response to both extracellular (extrinsic) and intracellular (intrinsic) signals. The extrinsic and intrinsic pathways are characterized by the formation of the death-inducing signaling complex (DISC) and the apoptosome, respectively; both the DISC and the apoptosome are oligomers with complex formation dynamics.
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Papers by Samik Ghosh