1. The document discusses systems biology approaches to modeling the endothelial cell response to fluid shear stress. It describes experimental techniques to apply controlled fluid shear stress and measure downstream cellular responses.
2. Mathematical models are formulated to represent molecular interactions and pathways involved in the shear stress response. Model predictions are compared to experimental data to validate and refine the models.
3. The models can provide insights into critical components, feedback loops, and how external perturbations may influence the cellular response to shear stress. Further experimental validation of model predictions is needed.
The NF-κB/Rel family consists of signal-responsive transcription factors that are activated by signals like cytokines and bacterial LPS. They exist as inactive complexes in the cytoplasm bound to inhibitory IκB proteins. Upon stimulation, IκB is degraded and NF-κB dimers translocate to the nucleus to activate target genes involved in immune, inflammatory, and stress responses. The family includes proteins containing Rel homology domains that form homo- and heterodimers and are regulated by two main signaling pathways, one dependent on IKKβ and the other on IKKα and NIK.
The NF-kB pathway is a transcription factor that controls DNA transcription and is considered a prototypical proinflammatory signaling pathway. It is composed of five related transcription factors that bind to DNA sequences called B sites to modulate gene expression. There are two NF-kB signaling pathways: the classical pathway activated by ligands binding to cell surface receptors and recruiting the IKK complex to activate NF-kB subunits, and the alternative pathway activated by ligands binding receptors and activating NIK which phosphorylates IKK to activate NF-kB subunits. NF-kB has implications in cancers, inflammation, immunity, development, and cell survival.
This document summarizes research on NF-kB signaling in cancer, specifically gastric cancer. It describes the background, structure and activation processes of NF-kB. Experiments show that NF-kB1 and RELA are upregulated in gastric cancer cell lines and tumors, and their knockdown inhibits tumor growth in vitro and in vivo. Furthermore, miR-508-3p is identified as a tumor suppressor that directly targets and downregulates NF-kB1 in gastric cancer. Re-expression of NF-kB1 partly reverses the tumor suppressive effects of miR-508-3p overexpression. In conclusion, downregulation of miR-508-3p contributes to canonical NF-kB activation in gastric tumorigenesis.
The document describes a novel family of biosensors called Nomad biosensors that can measure G protein-coupled receptor (GPCR) activity in living cells. Nomad biosensors detect changes in intracellular second messenger concentrations caused by GPCR activation. Depending on the second messenger involved in the GPCR pathway, there are three versions of Nomad biosensors that detect cAMP, calcium, or DAG. Nomad biosensors have been validated by expressing them in cells with several GPCRs and measuring changes in cytoplasmic granularity following receptor activation. They provide a sensitive method for high-throughput screening of drug libraries to identify compounds that modulate GPCR activity.
We previously reported a CRISPR-mediated knock-in strategy into introns of Drosophila genes, generating an attP-FRT-SA T2A-GAL4-polyA-3XP3-EGFP-FRT-attP transgenic library for multiple uses (Lee et al., 2018a). The method relied on double stranded DNA (dsDNA) homology donors with ~1 kb homology arms. Here, we describe three new simpler ways to edit genes in flies. We create single stranded DNA (ssDNA) donors using PCR and add 100 nt of homology on each side of an integration cassette, followed by enzymatic removal of one strand. Using this method, we generated GFP-tagged proteins that mark organelles in S2 cells. We then describe two dsDNA methods using cheap synthesized donors flanked by 100 nt homology arms and gRNA target sites cloned into a plasmid. Upon injection, donor DNA (1 to 5 kb) is released from the plasmid by Cas9. The cassette integrates efficiently and precisely in vivo. The approach is fast, cheap, and scalable.
This document discusses the role of NF-κB in regulating apoptosis. It describes how NF-κB is a transcription factor that regulates the expression of many anti-apoptotic genes. The regulation of NF-κB involves its interaction with the inhibitory protein IκB and transport between the cytoplasm and nucleus. Phosphorylation of IκB leads to its degradation and the release of NF-κB to enter the nucleus and activate gene transcription. This tight regulation of NF-κB activity and localization determines whether a cell survives or undergoes apoptosis.
1. The document discusses systems biology approaches to modeling the endothelial cell response to fluid shear stress. It describes experimental techniques to apply controlled fluid shear stress and measure downstream cellular responses.
2. Mathematical models are formulated to represent molecular interactions and pathways involved in the shear stress response. Model predictions are compared to experimental data to validate and refine the models.
3. The models can provide insights into critical components, feedback loops, and how external perturbations may influence the cellular response to shear stress. Further experimental validation of model predictions is needed.
The NF-κB/Rel family consists of signal-responsive transcription factors that are activated by signals like cytokines and bacterial LPS. They exist as inactive complexes in the cytoplasm bound to inhibitory IκB proteins. Upon stimulation, IκB is degraded and NF-κB dimers translocate to the nucleus to activate target genes involved in immune, inflammatory, and stress responses. The family includes proteins containing Rel homology domains that form homo- and heterodimers and are regulated by two main signaling pathways, one dependent on IKKβ and the other on IKKα and NIK.
The NF-kB pathway is a transcription factor that controls DNA transcription and is considered a prototypical proinflammatory signaling pathway. It is composed of five related transcription factors that bind to DNA sequences called B sites to modulate gene expression. There are two NF-kB signaling pathways: the classical pathway activated by ligands binding to cell surface receptors and recruiting the IKK complex to activate NF-kB subunits, and the alternative pathway activated by ligands binding receptors and activating NIK which phosphorylates IKK to activate NF-kB subunits. NF-kB has implications in cancers, inflammation, immunity, development, and cell survival.
This document summarizes research on NF-kB signaling in cancer, specifically gastric cancer. It describes the background, structure and activation processes of NF-kB. Experiments show that NF-kB1 and RELA are upregulated in gastric cancer cell lines and tumors, and their knockdown inhibits tumor growth in vitro and in vivo. Furthermore, miR-508-3p is identified as a tumor suppressor that directly targets and downregulates NF-kB1 in gastric cancer. Re-expression of NF-kB1 partly reverses the tumor suppressive effects of miR-508-3p overexpression. In conclusion, downregulation of miR-508-3p contributes to canonical NF-kB activation in gastric tumorigenesis.
The document describes a novel family of biosensors called Nomad biosensors that can measure G protein-coupled receptor (GPCR) activity in living cells. Nomad biosensors detect changes in intracellular second messenger concentrations caused by GPCR activation. Depending on the second messenger involved in the GPCR pathway, there are three versions of Nomad biosensors that detect cAMP, calcium, or DAG. Nomad biosensors have been validated by expressing them in cells with several GPCRs and measuring changes in cytoplasmic granularity following receptor activation. They provide a sensitive method for high-throughput screening of drug libraries to identify compounds that modulate GPCR activity.
We previously reported a CRISPR-mediated knock-in strategy into introns of Drosophila genes, generating an attP-FRT-SA T2A-GAL4-polyA-3XP3-EGFP-FRT-attP transgenic library for multiple uses (Lee et al., 2018a). The method relied on double stranded DNA (dsDNA) homology donors with ~1 kb homology arms. Here, we describe three new simpler ways to edit genes in flies. We create single stranded DNA (ssDNA) donors using PCR and add 100 nt of homology on each side of an integration cassette, followed by enzymatic removal of one strand. Using this method, we generated GFP-tagged proteins that mark organelles in S2 cells. We then describe two dsDNA methods using cheap synthesized donors flanked by 100 nt homology arms and gRNA target sites cloned into a plasmid. Upon injection, donor DNA (1 to 5 kb) is released from the plasmid by Cas9. The cassette integrates efficiently and precisely in vivo. The approach is fast, cheap, and scalable.
This document discusses the role of NF-κB in regulating apoptosis. It describes how NF-κB is a transcription factor that regulates the expression of many anti-apoptotic genes. The regulation of NF-κB involves its interaction with the inhibitory protein IκB and transport between the cytoplasm and nucleus. Phosphorylation of IκB leads to its degradation and the release of NF-κB to enter the nucleus and activate gene transcription. This tight regulation of NF-κB activity and localization determines whether a cell survives or undergoes apoptosis.
The document summarizes research on the polarized trafficking of neuronal proteins like syntaxins and potassium channels. It finds that syntaxin 3 mediates the trafficking of NgCAM to axons, while potassium channel Kir2.3 is clustered in dendritic spines through its interaction with PSD-95. Precise localization of proteins through trafficking mechanisms is important for neuronal polarity and function.
Calcium signaling plays a key role in many neuronal functions. It is involved in synaptic transmission, where calcium influx triggers neurotransmitter release from presynaptic terminals. Calcium also regulates neuronal development by specifying neurotransmitter phenotypes in developing neurons. Dysregulation of calcium homeostasis can lead to neurodegeneration or diseases associated with calcium channel defects. Many neurological disorders like Alzheimer's, Parkinson's, and Huntington's disease involve calcium dyshomeostasis.
This document summarizes research on converting an engineered potassium-binding site in cytochrome c peroxidase (CCP) into a calcium-selective site through protein engineering and crystal structure analysis. The researchers previously engineered a potassium-binding site in CCP based on the structure of ascorbate peroxidase. They then designed mutants intended to bind calcium selectively instead. The crystal structure of the first mutant showed binding of a smaller cation like sodium rather than calcium due to disordering of a ligand. A second mutant was then designed and its crystal structure confirmed calcium binding with a fully coordinated ligand environment, demonstrating that an iterative engineering approach can switch cation selectivity in proteins.
The document summarizes research on the Monascus genome project and related genetic studies. Key points include:
1) The Monascus genome was sequenced to 8x coverage, revealing various genomic features. A Monacolin K biosynthesis gene cluster was identified containing genes for polyketide synthases and other enzymes.
2) An efficient method for genetic transformation of Monascus pilosus was developed using aurintricarboxylic acid.
3) Disruption of the mokA gene and overexpression of the mokH transcription factor gene resulted in loss of and increased Monacolin K production, respectively.
This study examines the degradation pathway of the thiazide-sensitive NaCl cotransporter (NCC) in yeast and mammalian cells. The authors show that NCC is a substrate of endoplasmic reticulum-associated degradation (ERAD) in yeast. Using yeast strains with mutations in ERAD components, they identify the E3 ubiquitin ligase Hrd1 and the cytoplasmic Hsp70 chaperone Ssa1/Hsp70 as important for NCC ubiquitination and degradation. Expression of NCC in mammalian kidney cells reveals similar polyubiquitination and proteasome-dependent degradation. Cytoplasmic Hsp70 preferentially associates with immature glycosylated NCC, indicating its role
Innovations in Sequencing & Bioinformatics
Talk for
Healthy Central Valley Together Research Workshop
Jonathan A. Eisen University of California, Davis
January 31, 2024 linktr.ee/jonathaneisen
Presentation pathway extensions using knowledge integration and network approaches presented at the Systems Biology Institute in Luxembourg on November 28 2012.
The document discusses several key topics in biology including different philosophies of scientific discovery, evolutionary theory and computational analysis bridging approaches, complexity across levels of biological organization, and challenges in the scientific process. It provides examples of protein domain analysis illuminating relationships across life and computational analysis of biological networks. It also discusses sociological challenges around scientific competition, publication, and peer review that can hamper effective transmission of discoveries.
A family of acetylcholine-gated chloride channel subunits in Caenorhabditis e...Igor Putrenko
This document summarizes the cloning and characterization of acetylcholine-gated chloride channel subunits in Caenorhabditis elegans. The authors cloned four subunits, ACC-1, ACC-2, ACC-3, and ACC-4, which form a distinct clade of ligand-gated ion channel genes in C. elegans. They found that ACC-1 and ACC-2 form homomeric channels that are gated by acetylcholine but not nicotine, blocked by D-tubocurarine but not α-bungarotoxin, and conduct chloride ions. ACC-3 and ACC-4 may interact with ACC-1 and ACC-2. This study identifies the first molecular
RNA-Seq transcriptome analysis of Gonium pectorale cell cycleJennifer Shelton
This document summarizes an RNA-Seq analysis of the cell cycle transcriptome in the multicellular green alga Gonium pectorale. RNA was collected from G. pectorale cells across four time points in the cell cycle and sequenced. Differentially expressed genes were identified, including genes related to mitosis that were highly expressed at specific time points. Preliminary hierarchical clustering analysis grouped genes by expression patterns across the cell cycle. The goal is to compare the G. pectorale cell cycle transcriptome to Chlamydomonas to investigate changes in gene expression related to the evolution of multicellularity.
1) The study explores the role of plasma membrane calcium ATPase-4 (PMCA4) and its splice variants in vascular smooth muscle cell (VSMC) cell cycle progression.
2) It finds that the ratio of PMCA4a to PMCA4b splice variants decreases after arterial injury, and that PMCA4 knockout mice have reduced VSMC proliferation and G1 cell cycle arrest.
3) Rescue experiments show that both PMCA4a and PMCA4b can rescue this phenotype, indicating PMCA4 calcium efflux activity regulates G1 progression, though they may act through different downstream effectors.
RNA-Seq transcriptome analysis of Gonium pectorale cell cycle.Jennifer Shelton
This document summarizes Dr. Tara N. Marriage's RNA-Seq analysis of the cell cycle transcriptome in the multicellular alga Gonium pectorale. RNA was extracted from G. pectorale cells collected hourly across a 24 hour period and pooled into time points corresponding to different cell cycle phases. RNA-Seq libraries were constructed and sequenced, and the reads were mapped and analyzed for differential gene expression. Preliminary results identified over 2400 differentially expressed genes across the cell cycle and hierarchical clustering of expression profiles. Several key cell cycle genes were found to be differentially expressed during mitosis. The analysis is ongoing to further investigate cell cycle regulation and changes contributing to multicellularity in Gonium compared
Atherosclerosis is the buildup of plaque in artery walls due to injuries to the endothelial lining. Endothelial cells regulate blood flow through signal transduction and are sensitive to physical forces like shear stress from fluid movement. We developed a systems biology model with over 700 molecular reactions to investigate and predict how endothelial cells respond to shear stress at the molecular level. While our model matched some experimental data, it failed to capture other dynamics, suggesting there are still unknown interactions and responses that need to be incorporated.
OVium Bio-Information Solutions use forefront algorithms to analyze key data resources such NCBI, EBLM and PDB to develop cell signal pathways.
OVium employs cloud and MPP computing solutions with homology and signal network mapping to develop chemical and protein pathways for discovery research.
Endocytosis and Endosome Trafficking: Roles in Coronavirus Uptake and Cell Si...InsideScientific
To learn more and watch the webinar, visit:
https://insidescientific.com/webinar/endocytosis-endosome-trafficking-coronavirus-uptake-cell-signaling-aps
Endocytosis and Endosome Trafficking: Roles in Coronavirus Uptake and Cell Signaling
Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to share on Email (Opens in new window)
ON DEMAND
Ole Petersen, Roop Mallik and Erwin Neher share late-breaking research looking at endocytosis and calcium signaling in the context of SARS-CoV-2, organelle transport and calcium imaging. This webinar is brought to you by APS’ new journal, Function, and part of their Physiology in Focus learning series.
REGISTER
During this exclusive live webinar, Ole Petersen, Roop Mallik and Erwin Neher discuss how the COVID-19 virus uses receptor-mediated endocytosis to gain entry into host cells, how motor proteins guide endosomes and phagosomes from the cell surface to lysosomes, and how intracellular calcium buffering can be used to modulate cell signaling and calcium imaging.
Endocytic Uptake of SARS-CoV-2: The Critical Roles of pH, Ca2+ and NAADP
Ole Petersen, CBE, FRS
Very recent work shows that SARS-CoV-2 enters our cells through receptor-mediated endocytosis, dependent on an endosomal bafilomycin-sensitive proton pump as well as two-pore channels (TPCs). Physiological intracellular Ca2+ signals, mediated by the messenger nicotinic acid adenine dinucleotide phosphate (NAADP), depend on the very same proton pump and TPCs. Two hitherto completely separate research fields, namely molecular virology and cellular Ca2+ signaling physiology are now coming together, creating exciting new research opportunities.
Trafficking of Endosomes and Phagosomes: Geometry, Force and Cholesterol
Roop Mallik, PhD
Uptake of material from the external world by endocytosis/phagocytosis supplies nutrients to cells, and is also critical for cell signaling. The journey of endosomes/phagosomes begins at the cell periphery and ends at lysosomes near the cell center. I will discuss how the balance of forces generated by antagonistic motor proteins guides this journey, and how lipids are emerging as a master-controller of this balance.
Calcium Buffering in Endo- and Exocytosis Studies
Erwin Neher, FRS
Researchers use calcium-chelators (buffers) to manipulate levels of free intracellular calcium concentration ([Ca2+]i) and to shape Calcium signals. Unlike pH buffers, which are used to strictly control pH levels, calcium buffers inside a living cell may not influence the steady-state level of [Ca2+]i at all, but rather slow-down [Ca2+]i-changes induced either endogenously or by the experimenter. Such properties and their consequences on Ca2+-imaging will be discussed.
Bioinformatic data analysis – comparison from three human studies using diffe...Agnieszka Caruso
This document summarizes three bioinformatics studies comparing gene expression data from human samples using different Affymetrix platforms: 1) comparing periodontal ligament and gingival cells, 2) identifying genes regulated by nuclear IGFBP5 in osteoblasts, and 3) effects of LPS on osteoblasts. Key findings include identification of differentially expressed genes and biological processes between tissue types in study 1, and processes related to cell cycle, proliferation and splicing regulated by IGFBP5 in study 2. Study 3 on LPS effects found upregulation of factors stimulating osteoclasts and downregulation of processes like mitosis and cell cycle. The document discusses analysis tools and validation of array results.
The International Journal of Engineering and Science (IJES)theijes
The International Journal of Engineering & Science is aimed at providing a platform for researchers, engineers, scientists, or educators to publish their original research results, to exchange new ideas, to disseminate information in innovative designs, engineering experiences and technological skills. It is also the Journal's objective to promote engineering and technology education. All papers submitted to the Journal will be blind peer-reviewed. Only original articles will be published.
Microbial biosensors structure and mechanism Reza Khedmati
1) The document discusses the use of biosensors for detecting heavy metals using bioluminescent bacterial sensors. It describes how reporter genes like luciferase are induced by heavy metals, causing the bacteria to luminesce.
2) Methods of immobilizing bacteria in calcium alginate beads for use in biosensors are covered. The document also examines how biosensors can be used to test environmental samples and monitor toxicity over time and with reuse.
3) Detection techniques like colorimetric assays are discussed, where changes in color can indicate heavy metal presence without specialized instruments. The document evaluates biosensor performance in detecting various heavy metals in water and soil.
Using biological network approaches for dynamic extension of micronutrient re...Chris Evelo
This document discusses using biological network approaches to dynamically extend pathways with regulatory information such as microRNAs (miRNAs). It describes tools like PathVisio that can integrate gene expression, proteomics and metabolomics data onto pathways to identify significantly changed processes. WikiPathways is introduced as a public pathway resource that can be contributed to and curated by researchers. The document outlines approaches for visualizing regulatory interactions on pathways using plugins, exploring pathway interactions through network analysis, and integrating other data types such as SNPs, fluxes and gene annotations to build a more comprehensive understanding of biological systems.
1) Wnt3a protein rapidly increases the frequency of miniature excitatory synaptic currents in hippocampal neurons through a mechanism involving calcium influx and post-translational modifications enhancing vesicle exocytosis.
2) While previous studies suggested Wnt signaling modulates neurotransmission, this is the first to demonstrate a direct effect of a purified Wnt ligand, Wnt3a, on synaptic transmission.
3) The results identify Wnt3a and its receptor LRP6 as key molecules in neurotransmission modulation and suggest crosstalk between canonical and Wnt/calcium signaling in central neurons.
"Got a nail? I got a hammer": Lessons for data science from the "dawn" of big...Benjamin Keller
[presentation to Data Science Dojo meetup on 14 Jan 2015]
Years before anyone had uttered the words “data” and “science” together to mean a professional discipline, the NIH was funding the National Centers for Biomedical Computing. For five years, I was attached to one of these centers hosted at U.Michigan where scientists and computational experts were engaged in large projects attempting to explain complex phenomena in human disease by integrating the analysis of data and domain information. Rather than talk about the scientific success of this grand effort, I will discuss lessons from this experience that can guide us as we build our skills as data scientists and help others understand their data.
[Slides for presentation to STEAM Vent Meetup on Jan 8th, 2015.] Presents a (somewhat fictional) progression of ideas using graphs to analyze data, and how blindly following this progression leads to failed analysis because we did not consider supporting human reasoning as an end goal. Audience is general math and science knowledgeable group.
More Related Content
Similar to Graph Annotation: A Tale of Two Binary Relations
The document summarizes research on the polarized trafficking of neuronal proteins like syntaxins and potassium channels. It finds that syntaxin 3 mediates the trafficking of NgCAM to axons, while potassium channel Kir2.3 is clustered in dendritic spines through its interaction with PSD-95. Precise localization of proteins through trafficking mechanisms is important for neuronal polarity and function.
Calcium signaling plays a key role in many neuronal functions. It is involved in synaptic transmission, where calcium influx triggers neurotransmitter release from presynaptic terminals. Calcium also regulates neuronal development by specifying neurotransmitter phenotypes in developing neurons. Dysregulation of calcium homeostasis can lead to neurodegeneration or diseases associated with calcium channel defects. Many neurological disorders like Alzheimer's, Parkinson's, and Huntington's disease involve calcium dyshomeostasis.
This document summarizes research on converting an engineered potassium-binding site in cytochrome c peroxidase (CCP) into a calcium-selective site through protein engineering and crystal structure analysis. The researchers previously engineered a potassium-binding site in CCP based on the structure of ascorbate peroxidase. They then designed mutants intended to bind calcium selectively instead. The crystal structure of the first mutant showed binding of a smaller cation like sodium rather than calcium due to disordering of a ligand. A second mutant was then designed and its crystal structure confirmed calcium binding with a fully coordinated ligand environment, demonstrating that an iterative engineering approach can switch cation selectivity in proteins.
The document summarizes research on the Monascus genome project and related genetic studies. Key points include:
1) The Monascus genome was sequenced to 8x coverage, revealing various genomic features. A Monacolin K biosynthesis gene cluster was identified containing genes for polyketide synthases and other enzymes.
2) An efficient method for genetic transformation of Monascus pilosus was developed using aurintricarboxylic acid.
3) Disruption of the mokA gene and overexpression of the mokH transcription factor gene resulted in loss of and increased Monacolin K production, respectively.
This study examines the degradation pathway of the thiazide-sensitive NaCl cotransporter (NCC) in yeast and mammalian cells. The authors show that NCC is a substrate of endoplasmic reticulum-associated degradation (ERAD) in yeast. Using yeast strains with mutations in ERAD components, they identify the E3 ubiquitin ligase Hrd1 and the cytoplasmic Hsp70 chaperone Ssa1/Hsp70 as important for NCC ubiquitination and degradation. Expression of NCC in mammalian kidney cells reveals similar polyubiquitination and proteasome-dependent degradation. Cytoplasmic Hsp70 preferentially associates with immature glycosylated NCC, indicating its role
Innovations in Sequencing & Bioinformatics
Talk for
Healthy Central Valley Together Research Workshop
Jonathan A. Eisen University of California, Davis
January 31, 2024 linktr.ee/jonathaneisen
Presentation pathway extensions using knowledge integration and network approaches presented at the Systems Biology Institute in Luxembourg on November 28 2012.
The document discusses several key topics in biology including different philosophies of scientific discovery, evolutionary theory and computational analysis bridging approaches, complexity across levels of biological organization, and challenges in the scientific process. It provides examples of protein domain analysis illuminating relationships across life and computational analysis of biological networks. It also discusses sociological challenges around scientific competition, publication, and peer review that can hamper effective transmission of discoveries.
A family of acetylcholine-gated chloride channel subunits in Caenorhabditis e...Igor Putrenko
This document summarizes the cloning and characterization of acetylcholine-gated chloride channel subunits in Caenorhabditis elegans. The authors cloned four subunits, ACC-1, ACC-2, ACC-3, and ACC-4, which form a distinct clade of ligand-gated ion channel genes in C. elegans. They found that ACC-1 and ACC-2 form homomeric channels that are gated by acetylcholine but not nicotine, blocked by D-tubocurarine but not α-bungarotoxin, and conduct chloride ions. ACC-3 and ACC-4 may interact with ACC-1 and ACC-2. This study identifies the first molecular
RNA-Seq transcriptome analysis of Gonium pectorale cell cycleJennifer Shelton
This document summarizes an RNA-Seq analysis of the cell cycle transcriptome in the multicellular green alga Gonium pectorale. RNA was collected from G. pectorale cells across four time points in the cell cycle and sequenced. Differentially expressed genes were identified, including genes related to mitosis that were highly expressed at specific time points. Preliminary hierarchical clustering analysis grouped genes by expression patterns across the cell cycle. The goal is to compare the G. pectorale cell cycle transcriptome to Chlamydomonas to investigate changes in gene expression related to the evolution of multicellularity.
1) The study explores the role of plasma membrane calcium ATPase-4 (PMCA4) and its splice variants in vascular smooth muscle cell (VSMC) cell cycle progression.
2) It finds that the ratio of PMCA4a to PMCA4b splice variants decreases after arterial injury, and that PMCA4 knockout mice have reduced VSMC proliferation and G1 cell cycle arrest.
3) Rescue experiments show that both PMCA4a and PMCA4b can rescue this phenotype, indicating PMCA4 calcium efflux activity regulates G1 progression, though they may act through different downstream effectors.
RNA-Seq transcriptome analysis of Gonium pectorale cell cycle.Jennifer Shelton
This document summarizes Dr. Tara N. Marriage's RNA-Seq analysis of the cell cycle transcriptome in the multicellular alga Gonium pectorale. RNA was extracted from G. pectorale cells collected hourly across a 24 hour period and pooled into time points corresponding to different cell cycle phases. RNA-Seq libraries were constructed and sequenced, and the reads were mapped and analyzed for differential gene expression. Preliminary results identified over 2400 differentially expressed genes across the cell cycle and hierarchical clustering of expression profiles. Several key cell cycle genes were found to be differentially expressed during mitosis. The analysis is ongoing to further investigate cell cycle regulation and changes contributing to multicellularity in Gonium compared
Atherosclerosis is the buildup of plaque in artery walls due to injuries to the endothelial lining. Endothelial cells regulate blood flow through signal transduction and are sensitive to physical forces like shear stress from fluid movement. We developed a systems biology model with over 700 molecular reactions to investigate and predict how endothelial cells respond to shear stress at the molecular level. While our model matched some experimental data, it failed to capture other dynamics, suggesting there are still unknown interactions and responses that need to be incorporated.
OVium Bio-Information Solutions use forefront algorithms to analyze key data resources such NCBI, EBLM and PDB to develop cell signal pathways.
OVium employs cloud and MPP computing solutions with homology and signal network mapping to develop chemical and protein pathways for discovery research.
Endocytosis and Endosome Trafficking: Roles in Coronavirus Uptake and Cell Si...InsideScientific
To learn more and watch the webinar, visit:
https://insidescientific.com/webinar/endocytosis-endosome-trafficking-coronavirus-uptake-cell-signaling-aps
Endocytosis and Endosome Trafficking: Roles in Coronavirus Uptake and Cell Signaling
Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to share on Email (Opens in new window)
ON DEMAND
Ole Petersen, Roop Mallik and Erwin Neher share late-breaking research looking at endocytosis and calcium signaling in the context of SARS-CoV-2, organelle transport and calcium imaging. This webinar is brought to you by APS’ new journal, Function, and part of their Physiology in Focus learning series.
REGISTER
During this exclusive live webinar, Ole Petersen, Roop Mallik and Erwin Neher discuss how the COVID-19 virus uses receptor-mediated endocytosis to gain entry into host cells, how motor proteins guide endosomes and phagosomes from the cell surface to lysosomes, and how intracellular calcium buffering can be used to modulate cell signaling and calcium imaging.
Endocytic Uptake of SARS-CoV-2: The Critical Roles of pH, Ca2+ and NAADP
Ole Petersen, CBE, FRS
Very recent work shows that SARS-CoV-2 enters our cells through receptor-mediated endocytosis, dependent on an endosomal bafilomycin-sensitive proton pump as well as two-pore channels (TPCs). Physiological intracellular Ca2+ signals, mediated by the messenger nicotinic acid adenine dinucleotide phosphate (NAADP), depend on the very same proton pump and TPCs. Two hitherto completely separate research fields, namely molecular virology and cellular Ca2+ signaling physiology are now coming together, creating exciting new research opportunities.
Trafficking of Endosomes and Phagosomes: Geometry, Force and Cholesterol
Roop Mallik, PhD
Uptake of material from the external world by endocytosis/phagocytosis supplies nutrients to cells, and is also critical for cell signaling. The journey of endosomes/phagosomes begins at the cell periphery and ends at lysosomes near the cell center. I will discuss how the balance of forces generated by antagonistic motor proteins guides this journey, and how lipids are emerging as a master-controller of this balance.
Calcium Buffering in Endo- and Exocytosis Studies
Erwin Neher, FRS
Researchers use calcium-chelators (buffers) to manipulate levels of free intracellular calcium concentration ([Ca2+]i) and to shape Calcium signals. Unlike pH buffers, which are used to strictly control pH levels, calcium buffers inside a living cell may not influence the steady-state level of [Ca2+]i at all, but rather slow-down [Ca2+]i-changes induced either endogenously or by the experimenter. Such properties and their consequences on Ca2+-imaging will be discussed.
Bioinformatic data analysis – comparison from three human studies using diffe...Agnieszka Caruso
This document summarizes three bioinformatics studies comparing gene expression data from human samples using different Affymetrix platforms: 1) comparing periodontal ligament and gingival cells, 2) identifying genes regulated by nuclear IGFBP5 in osteoblasts, and 3) effects of LPS on osteoblasts. Key findings include identification of differentially expressed genes and biological processes between tissue types in study 1, and processes related to cell cycle, proliferation and splicing regulated by IGFBP5 in study 2. Study 3 on LPS effects found upregulation of factors stimulating osteoclasts and downregulation of processes like mitosis and cell cycle. The document discusses analysis tools and validation of array results.
The International Journal of Engineering and Science (IJES)theijes
The International Journal of Engineering & Science is aimed at providing a platform for researchers, engineers, scientists, or educators to publish their original research results, to exchange new ideas, to disseminate information in innovative designs, engineering experiences and technological skills. It is also the Journal's objective to promote engineering and technology education. All papers submitted to the Journal will be blind peer-reviewed. Only original articles will be published.
Microbial biosensors structure and mechanism Reza Khedmati
1) The document discusses the use of biosensors for detecting heavy metals using bioluminescent bacterial sensors. It describes how reporter genes like luciferase are induced by heavy metals, causing the bacteria to luminesce.
2) Methods of immobilizing bacteria in calcium alginate beads for use in biosensors are covered. The document also examines how biosensors can be used to test environmental samples and monitor toxicity over time and with reuse.
3) Detection techniques like colorimetric assays are discussed, where changes in color can indicate heavy metal presence without specialized instruments. The document evaluates biosensor performance in detecting various heavy metals in water and soil.
Using biological network approaches for dynamic extension of micronutrient re...Chris Evelo
This document discusses using biological network approaches to dynamically extend pathways with regulatory information such as microRNAs (miRNAs). It describes tools like PathVisio that can integrate gene expression, proteomics and metabolomics data onto pathways to identify significantly changed processes. WikiPathways is introduced as a public pathway resource that can be contributed to and curated by researchers. The document outlines approaches for visualizing regulatory interactions on pathways using plugins, exploring pathway interactions through network analysis, and integrating other data types such as SNPs, fluxes and gene annotations to build a more comprehensive understanding of biological systems.
1) Wnt3a protein rapidly increases the frequency of miniature excitatory synaptic currents in hippocampal neurons through a mechanism involving calcium influx and post-translational modifications enhancing vesicle exocytosis.
2) While previous studies suggested Wnt signaling modulates neurotransmission, this is the first to demonstrate a direct effect of a purified Wnt ligand, Wnt3a, on synaptic transmission.
3) The results identify Wnt3a and its receptor LRP6 as key molecules in neurotransmission modulation and suggest crosstalk between canonical and Wnt/calcium signaling in central neurons.
Similar to Graph Annotation: A Tale of Two Binary Relations (20)
"Got a nail? I got a hammer": Lessons for data science from the "dawn" of big...Benjamin Keller
[presentation to Data Science Dojo meetup on 14 Jan 2015]
Years before anyone had uttered the words “data” and “science” together to mean a professional discipline, the NIH was funding the National Centers for Biomedical Computing. For five years, I was attached to one of these centers hosted at U.Michigan where scientists and computational experts were engaged in large projects attempting to explain complex phenomena in human disease by integrating the analysis of data and domain information. Rather than talk about the scientific success of this grand effort, I will discuss lessons from this experience that can guide us as we build our skills as data scientists and help others understand their data.
[Slides for presentation to STEAM Vent Meetup on Jan 8th, 2015.] Presents a (somewhat fictional) progression of ideas using graphs to analyze data, and how blindly following this progression leads to failed analysis because we did not consider supporting human reasoning as an end goal. Audience is general math and science knowledgeable group.
Mathematics of Incidence (part 4): Lattice dependenciesBenjamin Keller
Motivated by a simple example of collaborative filtering from previous presentations, we look at what it means to be dependent and independent in formal concept analysis, and what the limitations are for deciding how "strong" a dependency might be. Along the way, we catch a glimmer of how association rules arise from the concept lattice, and get a hint that we might need some information theory.
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Dynamic policy enforcement is becoming an increasingly important topic in today’s world where data privacy and compliance is a top priority for companies, individuals, and regulators alike. In these slides, we discuss how LinkedIn implements a powerful dynamic policy enforcement engine, called ViewShift, and integrates it within its data lake. We show the query engine architecture and how catalog implementations can automatically route table resolutions to compliance-enforcing SQL views. Such views have a set of very interesting properties: (1) They are auto-generated from declarative data annotations. (2) They respect user-level consent and preferences (3) They are context-aware, encoding a different set of transformations for different use cases (4) They are portable; while the SQL logic is only implemented in one SQL dialect, it is accessible in all engines.
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2. Context: Systems story telling
want to help user understand relationships in data so that
they can construct stories about biological systems
How do we use biological information and data to go from a
list of genes to a story about how symptoms of a genetic
disease arise?
[ ]
3. Context: Systems Story Telling
Classification
Reasoning
Model-based
Reasoning
Narrative
Reasoning
(based on B. Mirel, Supporting cognition in systems biology analysis; findings on users’ processes and design
implications. Journal of Biomedical Discovery and Collaboration 2009; 4:1-17)
what of all this
is the right
stuff?
how does it fit
together?
how does it do
something?
what stories
does it tell?
4. Context: Systems Story Telling
Classification
Reasoning
Model-based
Reasoning
Narrative
Reasoning
individual
components
networks/
graphs of
components
system
fragments
“whole”
systems
roles
contextual
classes
Grouping
Patterns
Composition
5. Two kinds of binary relations
individual
components
networks/
graphs of
components
roles
contextual
classes
6. Two kinds of binary relations
component
component
annotation
component
Incidence relation
Graph
,( )
,( )
7. Grouping
Start with
- a network graph of genes, and
- contextual annotations for each
Want to visualize what goes together
[ saw this before in cytoscape.js presentation ]
8. Grouping (hypergraph visualization)
MeSH: Calcium
GO BP: Metal Ion Transport
GO MF: Gated Channel Activity
GO MF: Cation Channel Activity
GO MF: Voltage-Gated Ion Channel Activity
MeSH: Phosphorylation
MeSH: Signal Transduction
MeSH: Intercellular Signaling Peptides and Proteins
MeSH: Rats
MeSH: Nerve Tissue Proteins
MeSH Ion Channel Gating
CRKL
ANK3
CABP1
CACNA
2D4
CACNB
3
GNB1
PCBD1
RIMS1
PPM1A
PRKAC
A
RYR2
SRI
CACNA
1C
FAS
FADD
CNTN1
HOOK1
KCNC1
KCNC2
SMAD3
SMAD2
PIK3R1
SPTBN4
SCN1B
SCNN1
B
SCN2A
9. Simplified Groupings
MeSH: Calcium
GO MF: Voltage-Gated Ion Channel Activity
MeSH: Phosphorylation
MeSH: Intercellular Signaling Peptides and Proteins
MeSH: Nerve Tissue Proteins
MeSH Ion Channel Gating
CRKL
ANK3
CABP1
CACNA
2D4
CACNB
3
GNB1
PCBD1
RIMS1
PPM1A
PRKAC
A
RYR2
SRI
CACNA
1C
FAS
FADD
CNTN1
HOOK1
KCNC1
KCNC2
SMAD3
SMAD2
PIK3R1
SPTBN4
SCN1B
SCNN1
B
SCN2A
MeSH: Calcium
GO MF: Voltage-Gated Ion Channel Activity
MeSH: Phosphorylation
MeSH: Intercellular Signaling Peptides and Proteins
MeSH: Rats
MeSH: Nerve Tissue Proteins
CRKL
ANK3
CABP1
CACNA
2D4
CACNB
3
GNB1
PCBD1
RIMS1
PPM1A
PRKAC
A
RYR2
SRI
CACNA
1C
FAS
FADD
CNTN1
HOOK1
KCNC1
KCNC2
SMAD3
SMAD2
PIK3R1
SPTBN4
SCN1B
SCNN1
B
SCN2A
MeSH: Calcium
GO MF: Voltage-Gated Ion Channel Activity
MeSH: Signal Transduction
MeSH: Nerve Tissue Proteins
MeSH Ion Channel Gating
CRKL
ANK3
CABP1
CACNA
2D4
CACNB
3
GNB1
PCBD1
RIMS1
PPM1A
PRKAC
A
RYR2
SRI
CACNA
1C
FAS
FADD
CNTN1
HOOK1
KCNC1
KCNC2
SMAD3
SMAD2
PIK3R1
SPTBN4
SCN1B
SCNN1
B
SCN2A
MeSH: Calcium
GO MF: Voltage-Gated Ion Channel Activity
MeSH: Signal Transduction
MeSH: Rats
MeSH: Nerve Tissue Proteins
CRKL
ANK3
CABP1
CACNA
2D4
CACNB
3
GNB1
PCBD1
RIMS1
PPM1A
PRKAC
A
RYR2
SRI
CACNA
1C
FAS
FADD
CNTN1
HOOK1
KCNC1
KCNC2
SMAD3
SMAD2
PIK3R1
SPTBN4
SCN1B
SCNN1
B
SCN2A
MeSH: Calcium
GO BP: Metal Ion Transport
GO MF: Gated Channel Activity
GO MF: Cation Channel Activity
MeSH: Phosphorylation
MeSH: Intercellular Signaling Peptides and Proteins
MeSH: Nerve Tissue Proteins
MeSH Ion Channel Gating
CRKL
ANK3
CABP1
CACNA
2D4
CACNB
3
GNB1
PCBD1
RIMS1
PPM1A
PRKAC
A
RYR2
SRI
CACNA
1C
FAS
FADD
CNTN1
HOOK1
KCNC1
KCNC2
SMAD3
SMAD2
PIK3R1
SPTBN4
SCN1B
SCNN1
B
SCN2A
MeSH: Calcium
GO BP: Metal Ion Transport
GO MF: Gated Channel Activity
GO MF: Cation Channel Activity
MeSH: Phosphorylation
MeSH: Intercellular Signaling Peptides and Proteins
MeSH: Rats
MeSH: Nerve Tissue Proteins
CRKL
ANK3
CABP1
CACNA
2D4
CACNB
3
GNB1
PCBD1
RIMS1
PPM1A
PRKAC
A
RYR2
SRI
CACNA
1C
FAS
FADD
CNTN1
HOOK1
KCNC1
KCNC2
SMAD3
SMAD2
PIK3R1
SPTBN4
SCN1B
SCNN1
B
SCN2A
MeSH: Calcium
GO BP: Metal Ion Transport
GO MF: Gated Channel Activity
GO MF: Cation Channel Activity
MeSH: Signal Transduction
MeSH: Nerve Tissue Proteins
MeSH Ion Channel Gating
CRKL
ANK3
CABP1
CACNA
2D4
CACNB
3
GNB1
PCBD1
RIMS1
PPM1A
PRKAC
A
RYR2
SRI
CACNA
1C
FAS
FADD
CNTN1
HOOK1
KCNC1
KCNC2
SMAD3
SMAD2
PIK3R1
SPTBN4
SCN1B
SCNN1
B
SCN2A
MeSH: Calcium
GO BP: Metal Ion Transport
GO MF: Gated Channel Activity
GO MF: Cation Channel Activity
MeSH: Signal Transduction
MeSH: Rats
MeSH: Nerve Tissue Proteins
CRKL
ANK3
CABP1
CACNA
2D4
CACNB
3
GNB1
PCBD1
RIMS1
PPM1A
PRKAC
A
RYR2
SRI
CACNA
1C
FAS
FADD
CNTN1
HOOK1
KCNC1
KCNC2
SMAD3
SMAD2
PIK3R1
SPTBN4
SCN1B
SCNN1
B
SCN2A
computed with BLOSOM (Zhao L, Zaki MJ, Ramakrishnan N., KDD 2006, 827-832), support=5
10. Human-edited Groupings
MeSH: Calcium
GO BP: Metal Ion Transport
GO MF: Gated Channel Activity
GO MF: Cation Channel Activity
OR
MeSH Ion Channel Gating
MeSH: Phosphorylation
MeSH: Intercellular Signaling Peptides and Proteins
MeSH: Nerve Tissue Proteins
CRKL
ANK3
CABP1
CACNA
2D4
CACNB
3
GNB1
PCBD1
RIMS1
PPM1A
PRKAC
A
RYR2
SRI
CACNA
1C
FAS
FADD
CNTN1
HOOK1
KCNC1
KCNC2
SMAD3
SMAD2
PIK3R1
SPTBN4
SCN1B
SCNN1
B
SCN2A
MeSH: Calcium
GO BP: Metal Ion Transport
GO MF: Gated Channel Activity
GO MF: Cation Channel Activity
OR
MeSH Ion Channel Gating
MeSH: Signal Transduction
MeSH: Nerve Tissue Proteins
CRKL
ANK3
CABP1
CACNA
2D4
CACNB
3
GNB1
PCBD1
RIMS1
PPM1A
PRKAC
A
RYR2
SRI
CACNA
1C
FAS
FADD
CNTN1
HOOK1
KCNC1
KCNC2
SMAD3
SMAD2
PIK3R1
SPTBN4
SCN1B
SCNN1
B
SCN2A
“user” merged/deleted annotations
11. Formal Concept Analysis
GNB1
PRKACA
RatsCNTN1
PIK3R1
Animals
SMAD2
SMAD3
Calcium
Ankyrins
SPTBN4
CRKL
Cell Line
FADD
Phosphorylation
Ranvier's Nodes
Precipitin Tests
Signal Transduction
Nerve Tissue ProteinsRIMS1
Two-Hybrid System Techniques
Intracellular Signaling Peptides and Pr
• Algebraic approach to
studying data as
incidence relation b/w
objects and attributes
• Construct formal
concepts (biclusters)
• Relate to form formal
concept lattice
12. Formal Concept
CACNA1C
Ion transport protein
KCNC1
KCNC2
RYR2
SCN2A
Beta1 adrenergic receptor signaling pathway
CACNB3
GNB1
PRKACA
Beta2 adrenergic receptor signaling pathway
cation transport
CACNA2D4
SCN1B
SCNN1B
metal ion transport
channel activity
ion channel activity
gated channel activity
cation channel activity
alkali metal ion binding
calcium channel activity
voltage-gated channel activity
transmembrane transporter activity
voltage-gated ion channel activity
substrate specific channel activity
voltage-gated cation channel activity
ion transmembrane transporter activity
substrate-specific transporter activity
cation transmembrane transporter activity
passive transmembrane transporter activity
metal ion transmembrane transporter activity
substrate-specific transmembrane transporter activity
ANK3
RatsCNTN1
PIK3R1
Animals
SMAD2
SMAD3
CABP1
Calcium
SRI
Ankyrins
SPTBN4
CRKL
Cell Line
FADD
Myocardium
Jurkat CellsFAS
PPM1A Smad2 Protein
Phosphorylation
Ranvier's Nodes
Sodium Channels
Calcium Channels
Precipitin Tests
Protein Subunits
Ion Channel Gating
Signal Transduction
Nerve Tissue ProteinsRIMS1
Patch-Clamp Techniques
Sodium Channel Blockers
Calcium Channels, L-Type
Two-Hybrid System Techniques
Ryanodine Receptor Calcium Release Channel
Intracellular Signaling Peptides and Proteins
• Can view incidence
relation as bipartite graph
• A formal concept is a
biclique: a pair of vertices
(A,B) such that for each
object a in A there is an
edge (a,b) for every
attribute b in B
• Can construct as closure
13. Ex: Signal Transduction
Beta1 adrenergic receptor signaling pathway
GNB1
PRKACA
Beta2 adrenergic receptor signaling pathway
Rats
PIK3R1
Animals
SMAD2
SMAD3
Calcium
CRKL
Cell Line
FADD
Myocardium
Jurkat Cells
FAS
PPM1A
Smad2 Protein
Phosphorylation
Calcium Channels
Precipitin Tests
Protein Subunits
Ion Channel Gating
Signal Transduction
Two-Hybrid System Techniques
Ryanodine Receptor Calcium Release Channel
Intracellular Signaling Peptides and Proteins
14. Ex: Signal Transduction
Beta1 adrenergic receptor signaling pathway
GNB1
PRKACA
Beta2 adrenergic receptor signaling pathway
Rats
PIK3R1
Animals
SMAD2
SMAD3
Calcium
CRKL
Cell Line
FADD
Myocardium
Jurkat Cells
FAS
PPM1A
Smad2 Protein
Phosphorylation
Precipitin Tests
Signal Transduction
Two-Hybrid System Techniques
Ryanodine Receptor Calcium Release Channel
Intracellular Signaling Peptides and Proteins
25. Groupings (again)
• A simplified grouping is represented by a minimal
anti-chain in the concept lattice that best covers
objects (e.g., vertices)
• Heuristic:
a. generate concepts for individual annotations
b.for each, create chain by selecting subconcept with
most objects
c. select from chains such that vertex set is covered
32. Patterns
• Previous examples project annotations onto the graph
• For patterns, project the graph onto the annotations
• Can use lattice to find emergent schema (Banks et al.)
• One heuristic: for each edge (a1,a2) find concepts for
a1 and a2, and follow pair of chains upward, adding
edges for new objects, until cannot add more
Banks E, Nabieva E, Chazelle B, Singh M (2008) PLoS Comput Biol 4(10): e1000203
38. More…
• Could keep going …
• Possible to extract association rules, decision trees
and more from concept lattice and use these to
annotate functional relationships in graphs (which
again is something that has been done other ways)
• Also possible to work with multi-valued incidence
relations (e.g., numeric data)
39. Inspired and informed by working with
Barbara Mirel and
NCIBI DBP scientists at U.Michigan
40. Resources
B Ganter, R Wille. Formal Concept Analysis:
Mathematical Foundations, Springer-Verlag, 1999.
!
F Kriegel, Visualization of Conceptual Data with
Methods of Formal Concept Analysis. Thesis,
Technische Universität Dresden, 2012.
!
http://www.upriss.org.uk/fca/fca.html