The following headlines link to summaries of research published in past years. Using the filters in the navigation bar, you can filter the summaries by research area, disease or lab group.
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Pregnancy Health, from Bench to Bedside
ISB is leading a comprehensive clinical study to tease out the intricacies of pregnancy as it progresses from conception to postpartum. In collaboration with Magee-Womens Health, ISB is collecting an exhaustive set of maternal and fetal health parameters — digital health, physiological, behavioral/contextual, molecular, clinical, and medical imaging measures — from multiple modalities and over the course of gestation.
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Placenta and Preterm Birth
ISB is using systems biology to map molecular network dynamics in normal pregnancy, as well as study changes that occur in pregnancies with complications such as preterm birth. By using a systems approach, we hope to gain a more comprehensive understanding of pathological changes that occur in pregnancy, and identify women most at risk of developing pregnancy complications.
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Method Developed to Profile Pathogen Gene Expression from Infected Host Cells
The rise in multi-drug resistant and extremely drug resistant strains of Mycobacterium tuberculosis has become a major cause of global health concern for treating tuberculosis. ISB researchers developed Path-seq, a method that profiles host and pathogen gene expression and can explore the pathogen transcriptome in vivo.
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Wilke Cohen Lyme Disease Project
ISB researchers have put their efforts into looking at Lyme disease and the bacteria, Borrelia burgdorferi, that causes the disease, through the lens of systems biology, and utilizing approaches pioneered at ISB to gather, synthesize and interpret large and complex datasets.
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Stress Test Predicts How Diatoms Will React to Ocean Acidification
The foundation of many marine food webs in which corals, fish and whales depend on are microscopic photosynthetic algae called diatoms. ISB scientists have developed a stress test to quantify and predict how ocean acidification would impact the resilience of diatoms in the future.
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Ultrafast Comparison of Personal Genomes
Genome sequences contain information with immense possibilities for research and personalized medical care, but their size, complexity and diversity make comparing sequences error-prone and slow. ISB researchers have created a method for summarizing a personal genome as a “fingerprint.”
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Pioneer 100 Study Establishes Foundation for New Industry of Scientific Wellness
Results from the Pioneer 100 Wellness Project, a nine-month study of 108 individuals, demonstrated that combining personal, dense, dynamic data clouds with tailored behavioral coaching can optimize wellness for individuals. These data clouds also can identify early transitions into disease states and facilitate the reversal of some disease states back to wellness.
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Identification of the proteins in Plasmodium vivax provide new targets for a malaria vaccine
Scientists from ISB and the Center for Infectious Disease Research led an international collaboration to identify proteins in the malaria parasite Plasmodium vivax. P. vivax and P. falciparum cause the majority of malaria cases, but P. vivax is far less-studied, in part because it cannot be grown in the lab. The research aims to provide new targets for a malaria vaccine.
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How Microbes Learn to Predict the Future
Like plants and animals, even microbes can anticipate and prepare in advance for future changes in their environment
Similar to how Pavlov trained a dog to anticipate food when it heard a bell, ISB researchers trained yeast to anticipate a lethal toxin when it sensed caffeine
The study revealed how in a very short period of time yeast can evolve to ‘learn’ and ‘predict’ new patterns in their environment -
TCGA Researchers Identify Potential Drug Targets for Leading Form of Deadly Liver Cancer
ISB researchers and colleagues from TCGA Research Network performed the first large-scale, multi-platform analysis of hepatocellular carcinoma, the predominant form of liver cancer. Such integrated analyses enabled the identification of potential therapeutic targets and facilitated biological insights that would not have been possible otherwise.
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A Cell-Surface Membrane Protein Signature for Glioblastoma
Using integrated protein and gene expression data, ISB researchers developed a 33-gene signature for glioblastoma, an aggressive form of brain cancer.
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ISB Scientists Have Discovered When and Why a Microbial Community Might Collapse
Researchers at Institute for Systems Biology have developed a framework for assessing the “health” of a microbial community through a stress test that enables them to ask when and why microbial communities collapse under different environmental conditions.
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Novel clustering algorithm identifies functional mutations in cancer genes
In a study published in PLoS Computational Biology, researchers at Institute for Systems Biology (ISB) have developed a multiscale mutation clustering algorithm (M2C) that identifies variable length regions with high mutation density in cancer genes.
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Mapping the early effects of the Huntington’s disease mutation in mice
A multi-institute collaboration sought to map in high-resolution the earliest effects of the Huntington’s disease mutation in mice.
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Introduce One-cell Doubling Evaluation of Living Arrays of Yeast! ODELAY!
Genes, Genomes, Genetics, scientists at Institute for Systems Biology introduce ODELAY, a powerful automated and scalable growth analysis platform that uses time-lapse microscopy to photograph individual yeast cells growing into colonies.
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Predicting Cell Fate Decisions Using Single-Cell Analysis and the Theory of Tipping Points
ISB researchers developed a new theory to exploit burgeoning single-cell molecular profiling measurements to make predictions of future cell behaviors.
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Proteomics: Identifying Organ-Specific Blood Biomarkers for Acute Liver Injury
To assess probable injury to an organ, it is important to monitor biologic materials that originate exclusively or primarily in that organ, in this case, liver-enriched proteins.
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Quantitating the Complete Human Proteome
ISB scientists collaborate with ETH Zurich to develop the Human SRMAtlas, a compendium of mass spectrometry assays for any human protein.
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Stitching Together Insight For Deadly Brain Cancer Glioblastoma
Using data from TCGA and ENCODE, ISB researchers developed an integrative database and analysis platform that provides insight into the underpinnings of glioblastoma multiforme, and identified a never before seen association between increased levels of immune molecules, tumor immune cell infiltration, and decreased patient survival.
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Speeding Up Drug Discovery to Fight Tuberculosis
Researchers at the Institute for Systems Biology and Center for Infectious Disease Research have deciphered how the human pathogen Mycobacterium tuberculosis is able to tolerate the recently approved FDA drug
The study demonstrated that silencing certain regulatory genes in the bacteria, or pairing with a second drug pretomanid, disrupts a tolerance gene network to improve efficacy of killing by bedaquiline.
This systems-approach to rational drug discovery represents significant advance in the fight against tuberculosis, which affects a third of the global population, surpassing HIV/AIDS in the number of deaths worldwide. -
Integrative Study of Rare Adrenocortical Carcinoma Reveals Prognostic Molecular Subtypes
Adrenocortical carcinoma (ACC) is a rare endocrine cancer with limited therapeutic options and overall poor outcome. In TCGA (The Cancer Genome Atlas) research published on May 9, 2016, in the journal Cancer Cell, scientists, including several from Institute for Systems Biology, comprehensively analyzed 91 ACC specimens from four continents using state-of-the-art genomic technologies and computational methods. The goal of the study was to identify additional oncogenic alterations to provide a framework for further research and guide development of therapies.
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Scratching the Surface of the Malaria Parasite
Surface coat proteins on Plasmodium, the parasite that causes malaria, provide new targets for a malaria vaccine. ISB scientists collaborate with scientists from Center for Infectious Disease Research and Johns Hopkins University to identify new proteins on the surface of the malaria parasite Plasmodium.
The research aims to provide new targets for a malaria vaccine.
It is discovered that some Plasmodium surface proteins have sugar attachments that can cloak these proteins from the human immune system. -
Genomic Architecture of Inflammatory Bowel Disease in 5 Families with Multiple Affected Individuals
In medical genetics it is an unsolved question to what degree complex diseases (such as inflammatory bowel disease) are influenced by rare variants with potentially large effects in relation to the many common and weak-effect variants that have been identified in genome-wide association studies (GWAS).
By analyzing whole-genome sequences of five families with a high burden of inflammatory bowel disease (IBD) we aimed to elucidate the genomic architecture of IBD.
We identified rare candidate variants and followed up one of them, a novel missense variant in TRIM11. We found evidence that the variant may foster IBD development by increasing inflammatory signaling in the gut. -
Ötzi the Iceman: Helicobacter pylori Pathogen Found in Stomach Contents
Institute for Systems Biology collaborates with researchers worldwide to study pathogens in the stomach content and microbiome of the 5300 year old European Copper Age glacier mummy “Ötzi” and discovers a Helicobacter pylori pathogen genome.
Ötzi harbored a nearly pure Asian-origin bacterial population of H. pylori providing key information as to population migration into Europe over the last few thousand years.
Supported by proteome information gathered at ISB, the Iceman’s stomach was found to be colonized by a cytotoxic strain of H. pylori that triggered host inflammation immune responses. -
Microalgae As Biofactories of a Sustainable Future
In an effort to better understand the gene regulatory and metabolic networks of the single-celled alga Chlamydomonas reinhardtii, researchers at Institute for Systems Biology studied the changes in Chlamy’s genetics and metabolism that cause them to capture and store carbon dioxide.
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Progress & Opportunities for Metabolic Reconstruction
In this study, we looked for evidence of such convergence through comparative analysis of 12 genome-scale yeast models.
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Prostate Cancer Study Identifies Numerous Subtypes of the Disease
Prostate cancer is the second most common cancer in men worldwide. The clinical behavior of prostate cancer is variable with some men exhibiting indolent prostate cancer which can be monitored over time while other men develop aggressive prostate cancer which can lead to metastasis and death.
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A Multilevel Pan-cancer Map Links Gene Mutations to Cancer Hallmarks
In the scientific community, cancer is not considered a single disease but a multitude of diseases. Different genes and molecular pathways have been associated with different types of cancer. These differences at the molecular level are being leveraged to enable personalized treatment regimes for cancer patients.
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Researchers determine architecture of a macromolecular complex regulating gene expression and DNA repair
The expression, or transcription, of genes controls the identity and function of a cell. DNA damage caused by UV light or other carcinogens must be repaired to maintain genome integrity. The general transcription factor TFIIH plays central roles in both processes and is also important to couple gene transcription with DNA repair. Researchers at the Institute for Systems Biology, in collaboration with the University of California, San Francisco, the University of Colorado Boulder, and the Fred Hutchinson Cancer Research Center, have mapped the architecture of the multi-subunit TFIIH complex. This research, published online in Molecular Cell on Sept. 4, 2015, represents a breakthrough in understanding the structural basis for transcription and DNA repair, and provides critical insights into how disruption of the TFIIH complex can lead to cancer and other diseases.
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Project Feed 1010 – Sustainable Agriculture
ISB is actively working on Project Feed 1010, a demonstration project and laying the experimental, computational, cloud-computing and social networking infrastructure for a first-of-its-kind network of farmers, scientists and educators to crowdsource sustainable agriculture research and education.
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100K Wellness Project
The Institute for Systems Biology (ISB) pioneered and has been recognized as the world leader in the systems approach to studying biology for the past 15 years. Guided by the vision of Dr. Lee Hood, ISB’s president and co-founder, ISB has also pioneered the concept of P4 Medicine (personalized, predictive, preventive, and participatory). This combination of a systems biology approach with P4 Medicine led to ISB launching in 2014, and completing in 2015, a pilot study called the Hundred Person Wellness Project (HPWP).
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Cancer Genomics Cloud
The ISB Cancer Genomics Cloud:
Leveraging Google Cloud Platform for TCGA Analysis
The ISB Cancer Genomics Cloud (ISB-CGC) is one of three pilot projects funded by the National Cancer Institute with the goal of democratizing access to the TCGA data by substantially lowering the barriers to accessing and computing over this rich dataset. The ISB-CGC is a cloud-based platform that will serve as a large-scale data repository for TCGA data, while also providing the computational infrastructure and interactive exploratory tools necessary to carry out cancer genomics research at unprecedented scales. The ISB-CGC will also facilitate collaborative research by allowing scientists to share data, analyses, and insights in a cloud environment. -
A Mixture of Markers from Two Distinct Cell Types Indicates Poor Prognosis in Breast Cancer
Metastatic breast cancer remains an incurable disease and has stimulated the search for the most aggressive cell types in the tumors that drive metastasis. These cells have long been thought to possess stem-cell character, hence the idea of Cancer Stem Cells, or CSCs.
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Genetic Switch May Help Marine Microalgae Respond to Higher CO2 Levels
Rapid climate change, including ocean acidification caused by increasing carbon dioxide (CO2) levels, is predicted to affect the oceans, sea life, and the global carbon cycle.
Marine microalgae, including diatoms, are responsible for converting CO2 into oxygen and biologically usable carbon through photosynthesis. How these organisms will respond over the short and long term to rising CO2 is unknown.
Growth experiments and transcriptomic analyses performed by UW and ISB researchers showed that the model diatom Thalassiosira pseudonana respond to increasing CO2 by down-regulating gene clusters involved in carbon concentrating mechanisms (CCMs) and photorespiration. It is hypothesized that this acclimation may allow diatoms to conserve energy at moderately increased CO2 levels, with implications for shifts in the composition and productivity of marine microbial ecosystems. -
Most Powerful Tool for Reconstructing a Gene Network
Nearly a decade ago, ISB’s Baliga Lab published a landmark paper describing cMonkey, an innovative method to accurately map gene networks within any organism from microbes to humans.
Two new papers describe the benchmark results of cMonkey and also the release of cMonkey2, which performs with higher accuracy.
Using this approach, genetic and molecular data generated from any organism, be it a bacterium or a birch tree, can be explored and analyzed from a network perspective. -
A Global Map To Fight Tuberculosis
The disease progression of tuberculosis is extremely complex and it’s poorly understood.
ISB and Seattle BioMed researchers have made an important step by developing a comprehensive map of gene regulation in tuberculosis.
A resulting open-access web portal offers any scientist the ability to mine the collected data. -
ISB Releases Open-Source Software to Analyze Digital Fingerprint of Protein Data
SWATH mass spectrometry, an emerging protein analysis technique being pioneered by ISB researchers, provides a digital fingerprint of all accessible proteins in a sample.
The data generated by the SWATH technique are highly complex and require sophisticated computational tools in order to extract identities from a sea of data.
ISB researchers have released a free, open source program that allows users to confidently identify and quantify proteins analyzed by SWATH -
Identifying markers of healthy skin development
The barrier function of skin is integral to personal well-being and is associated with several widespread diseases such as eczema and psoriasis.
ISB and Procter & Gamble researchers used human skin grown in the lab to measure changes in protein levels as the skin matures.
The results of this study provide many new markers for healthy skin development. -
Found: Key Protein Tied to ‘Good’ Cholesterol
Inflammation causes cholesterol buildup and leads to cardiovascular disease, the leading cause of death in the world
ISB, Seattle Biomed, and Oregon State University researchers collaborate to identify a compendium of proteins that control expression of a key regulator of cholesterol efflux
Targeting cholesterol efflux to HDL is a potentially important therapeutic strategy for preventing and treating cardiovascular disease -
A Universe Under the Microscope
It may seem strange to begin a prognostication for microbiology with a quote from an astronomer, but the two topics are more closely linked than appears at first glance. For starters, both fields were revolutionized around the same time, in the 17th century, with drastic improvements to the telescope and the compound microscope.
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Understanding the Genetic ‘Architecture’ of Bipolar Disorder
Bipolar disorder (BD) is a common, severe and recurrent psychiatric disorder with no known cure and substantial morbidity and mortality. Heritable causes contribute up to 80 percent of lifetime risk for BD.
Scientists hope that identifying the specific genes involved in risk for bipolar disorder will lead to new ways to treat the disease.
ISB researchers identified contributions of rare variants to BD by sequencing the genomes of 200 individuals from 41 families with BD. -
Network Representations of Immune System Complexity
The mammalian immune system is a dynamic multiscale system composed of a hierarchically organized set of molecular, cellular, and organismal networks that act in concert to promote effective host defense. These networks range from those involving gene regulatory and protein–protein interactions underlying intracellular signaling pathways and single-cell responses to increasingly complex networks of in vivo cellular interaction,
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ISB Releases Kaviar, World’s Largest Public Catalog of Human Genomic Variation
Kaviar is ISB’s comprehensive catalog of human genomic variation
Kaviar combines 31 data sources for a total of 151 million single nucleotide variants (SNVs), covering 5% of all the positions in the human genome
A researcher studying possible disease-causing variants can use Kaviar to answer the question, “Have these variants been observed before, and if so, how often?” -
Into the Genetic Weeds of Hair Growth
ISB researchers used a data-driven mathematical model to identify specific genes associated with hair regeneration.
Novel methodology paves way for continued research into the molecular basis of this complex cycle as well as other regenerative organs like skin and liver.
Findings may lead to more precise targets for therapies and genetic markers of hair wellness. -
Pushing the Molecular Switches of Tuberculosis Into Overdrive
Mycobacterium tuberculosis (MTB) infects more than 1.5 billion people worldwide partly due to its ability to sense and adapt to the broad range of hostile environments that exist within hosts.
To study how MTB controls its responses at a molecular level, ISB researchers and their collaborators at Seattle Biomed perturbed almost all MTB transcription factor regulators and identified the affected genes.
This comprehensive map of molecular switches in MTB provides a basis for understanding control mechanisms and can inform future efforts to rewire MTB responses for more favorable disease outcomes. -
Let Us Tell You Everything We Know About Proteomics – Everything
Proteomics experiments generate huge amounts of raw data, most of which cannot be easily shared or described in a publication.
ISB researchers curate publicly accessible databases that allow researchers to share their data with the world and to use data others have collected.
All data are analyzed in a consistent manner and results are presented via searchable, user-friendly web applications. -
How One Family of Microbial Genes Rewires Itself for New Niches
When an organism duplicates its genes, it increases its ability to adapt and colonize new environments.
ISB researchers used the systems approach to study how one family of microbial genes evolved to bring functions that were adaptive to specific environments.
This new understanding of how gene regulatory networks rewire themselves has many potential applications, including how to wire new functions into an organism for biofuel production, bio-remediation or bio-pharmaceutical production. -
What’s the Secret to ‘Extreme Longevity’?
ISB researchers and their collaborators studied a group of supercentenarians (110 years or older) to explore the genetics of ‘extreme longevity.’
The group performed whole-genome sequencing on 17 supercentenarians in order to look for any rare protein-altering variants associated with extreme longevity.
While the researchers did not find a single cause for extreme longevity within this sample size, the genomic data is now available for future studies. -
How Physics and Thermodynamics Help Assess DNA Defects in Cancer
‘Big data’ cancer research has revealed a new spectrum of genetic mutations across tumors that need understanding.
Existing methods for analyzing DNA defects in cancer are blind to how those mutations actually behave.
ISB scientists developed a new approach using physics- and structure-based modeling to systematically assess the spectrum of mutations that arise in several gene regulatory proteins in cancer. -
A New Approach to Identifying How the Deadly Dengue Virus Multiplies
Dengue virus is the most prevalent mosquito-borne virus worldwide, infecting an estimated 400 million people per year and causing about 25,000 deaths.
It’s necessary to understand the molecular mechanisms of dengue replication in order to develop an effective treatment.
Researchers at ISB and Seattle BioMed developed a novel approach for identifying host proteins that associate with dengue replication machinery. -
New Details on Thyroid Cancer May Lead to More Precise Therapies
Papillary thyroid cancer represents 80 percent of all thyroid cancer cases.
Integrative analysis resulted in the detection of significant molecular alterations not previously reported in the disease.
ISB researchers identified microRNAs which may lead to more precise therapy. -
New Tool Uses 3-D Protein-DNA Structures to Predict Locations of Genetic ‘On-Off’ Switches
Novel systems approach uses high-resolution structures of protein-DNA complexes to predict where transcription factors (genetic switches) bind and regulate the genome.
This approach can help researchers better understand and predict binding sites for non-model organisms or ‘exotic’ species.
Having such insight and predictive capabilities is critical for reverse- and forward-engineering organisms that could be pivotal for new green biotechnologies. -
Uncovering the Genetic Adaptability of Tuberculosis
The Institute for Systems Biology and Seattle BioMed have collaborated to reconstruct the gene regulatory network of the human pathogen Mycobacterium tuberculosis.
Finely tuned gene regulation has allowed Mycobacterium tuberculosis to survive unnoticed in an apparently healthy host for decades; understanding those subtleties is critical for advancing treatment.
The identification of co-regulated sets of genes and their regulatory influences offers validated predictions that will help guide future research into Mycobacterium tuberculosis pathogenicity. -
Analyzing Family Genomics Reveals New Culprit in Rare Disease
Adams-Oliver syndrome (AOS) is a rare congenital disease characterized by scalp lesions and limb defects. Additional vascular abnormalities and heart defects can lead to early death in some patients.
By analyzing twelve families affected with the disease, we identified causal mutations in a new disease gene, NOTCH1, in five families. NOTCH1 is likely to be the major cause of AOS.
NOTCH1 codes for a transcription factor that governs cell differentiation during embryonic development and throughout life. -
New Structural Map Helps To Understand Aggressive Tumors
Aggressive tumor growth is linked to high activity of a macromolecular assembly called RNA polymerase I.
ISB and FHCRC researchers collaborate to map the architecture of the assembly using a powerful crosslinking-mass spectrometry (CXMS) technology.
Structural maps provide important insights into therapeutic targets for cancer treatment. -
BIOCELLION: New Supercomputer Software Framework Models Biological Systems at Unprecedented Scales
Computer simulation is a promising way to model multicellular biological systems to help understand complexity underlying health and disease.
Biocellion is a high-performance computing (HPC) framework that enables the simulation of billions of cells across multiple scales.
Biocellion facilitates researchers without HPC expertise to easily build and simulate large models. -
Identifying Four New Subtypes of Gastric Cancer That May Lead to New Targeted Treatments
Gastric cancer has a high mortality rate, but current classification systems haven’t been effective in helping to identify subtypes relevant for treatment of the disease.
TCGA researchers have integrated molecular data from 295 stomach tumors and have discovered four subtypes of gastric cancer.
Stratification of patients into these four subtypes paves the way for the development of new personalized therapies. -
New Open-Access Multiscale Model Captures Dynamic Molecular Processes in Unprecedented Detail
Microbes are efficient because their streamlined genomes allow them to evolve and adapt rapidly to complex environmental changes.
Decoding the highly-compressed information within a microbial genome requires sophisticated systems biology tools to map the genetic programs, and understand how they are executed.
ISB researchers invented novel algorithms to unzip and decode microbial genomes into the EGRIN 2.0, an open-access multiscale model that captures instructions for executing the dynamic molecular processes in unprecedented detail. -
New Protein Modification Critical to Growth of Tuberculosis Pathogen Found
Institute for Systems Biology and Seattle BioMed researchers collaborated and discovered a new protein post-translational modification in the human pathogen Mycobacterium tuberculosis.
Post-translational modifications are essential mechanisms used by cells to diversify protein functions and ISB scientists identified the rare phosphorylated tyrosine post translational modification on Mycobacterium tuberculosis proteins using mass spectrometry.
Inhibiting phosphotyrosine modified amino acids in Mycobacterium tuberculosis severely limits the growth of this widespread deadly pathogen. -
Now researchers can explore genomic data across space and time
Understanding systems from a multiscale perspective gives us a more detailed and holistic view of how features or functions from each scale connect and interact in a given system.
The challenge is integrating the different types of information that come from each scale in an efficient way that yields the most insight.
ISB developed a new tool to make it easier for researchers to to integrate, analyze and visualize human genome data at multiple resolutions. -
The Rise of Open Proteomics
Researchers at EMBL-EBI, Institute for Systems Biology and other partnering organizations have launched ProteomeXchange, a public portal for exchanging proteomics data generated from mass-spectrometry experiments and other related information.
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‘Demystifying Disease, Democratizing Health Care’
In Science Translational Medicine, Dr. Lee Hood and Dr. Nathan Price, of Institute for Systems Biology, deliver an editorial stating the vision of the 100K Wellness Project. The project will track health-related data types for 100K individuals longitudinally over the course of 20-30 or more years.Dr. Lee Hood and Dr. Nathan Price, of Institute for Systems Biology, deliver an editorial stating the vision of the 100K Wellness Project. The project will track health-related data types for 100K individuals longitudinally over the course of 20-30 or more years.
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Unpredictable Environments Require Predictably Fast Responses
ISB researchers discover a novel mechanism used by cells to rapidly turn “on” or “off” genes in order to change survival strategies in response to environmental events.
The “switch” was discovered in Halobacterium salinarium and found to be conserved in diverse life forms.
Research shows that microbes may use specialized switches depending on the type of environmental challenge they encounter. -
Tiniest Malfunctions in a Cell Can Cause Devastating Diseases
ISB researchers are studying peroxisomes, which are cellular organelles that are linked to a rare syndrome that causes progressive organ complications and infant mortality.
Peroxisomes have a role in metabolizing and breaking down cellular waste.
Because peroxisomes easily change shape and function according to a cell’s needs, a systems approach is necessary to help decipher that complexity. -
Matters of the Head and the Heart
Previous links between posttraumatic stress disorder (PTSD) and cardiovascular disorders were mostly thought to be psychological.
Using mouse models, researchers at ISB and U.S. Army Center for Environmental Health Research found physical injury of heart tissue as a result of exposure to stressful environments.
This research is important for developing future methods for early and objective diagnosis, and new therapeutic approaches for patients with PTSD and PTSD-associated ailments. -
Powerful New Program Integrates Multiple Tools Into a Flexible Interface
Price Lab researchers worked with collaborators at the University of Illinois to create an easy-to-use software toolkit for comparing microbial genomes.
Tools can be used to find orthologs, correct missing/inaccurate gene annotations, analyze gene gain and loss patterns, and build draft metabolic networks from reference networks.
Software offers predictive and analysis capabilities in a flexible way, making it easy to build customized analysis pipelines. -
50 Years in the Lab Doesn’t Diminish an Organism’s Memory of Its Natural Environment
ISB researchers discover that microbes retain complex survival traits despite having been domesticated for more than 50 years.
Study reveals that gene networks store a historic record of environmental change.
Research reinforces the concept that model organisms can serve as authentic systems to study evolution of complex traits. -
The Bug Stops Here: Arresting Malaria Parasites in the Liver Gives Immunity
ISB researchers collaborated with Seattle BioMed researchers to identify molecular building blocks required by malaria parasites to build cell membranes.
Deleting key genes necessary for building cell membranes created a parasite that does not make the host sick and can’t be passed on through the blood.
Treating mice with modified parasites gave them complete immunity against malaria. -
Participatory Medicine is Revolutionizing Healthcare
Dr. Lee Hood and his colleague Dr. Charles Auffray, of the European Institute for Systems Biology & Medicine, published an editorial in Genome Medicine. Healthcare is undergoing a profound revolution as a consequence of three contemporary thrusts: systems medicine, big data and patient involvement in their own health through social networks. This convergence is leading to a medicine that is predictive, preventive, personalized and participatory (P4).
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ISB Researchers Develop New Method to Study and Predict Traits of Cells
ISB researchers used the systems approach to develop a new way to integrate data from different classes of networks to better understand how cells function.
The method is a software program called GEMINI and it’s the first of its kind to integrate data from metabolic networks to refine transcriptional regulatory networks.
GEMINI has higher success rate than existing technologies. -
ISB’s PeptideAtlas Helps Advance the Study of Proteins
The Human Proteome Project expands on the work of the Human Genome Project.
ISB is a leader in proteomics and developed PeptideAtlas, a project that has cataloged the proteins observed in thousands of proteomics experiments as an open resource for researchers everywhere.
In a new report, ISB researchers show that PeptideAtlas now contains proteins from about 62 percent of human genes thought to encode proteins. -
A ‘Sound Check’ for Digital Transcriptomes
Looking for biomarkers in different types of tissues requires comparing massive amounts of gene expression data.
In order to compare ‘digital transcriptome’ data, they have to be normalized or adjusted to a common standard of measurement.
ISB researchers developed new algorithmic methods that outperform existing methods for normalizing gene expression data from different samples. -
How ISB’s Systems Approach Finds New Biological Insight from Existing Big-Data Sets
There exist copious amounts of public research data that can reveal new biological information if they are integrated and analyzed.
One of ISB’s specialties is the ability to apply systems approaches to develop methods to integrate and analyze data.
In the latest publication, ISB demonstrates an open-access computational strategy that can help any researcher capitalize on large data sets. -
Systems Approach to Innovation Helps Extract More Data
Technology lag affects the study of proteins, which when quantified can indicate disease or wellness.
ISB uses systems approach to innovate and transcend technology limitations.
ISB co-develops new technique and software suite to increase protein detection rate. -
Blood Test Helps Identify Benign Lung Nodules
When it comes to determining whether lung nodules are benign, a patient typically faces surgery and a biopsy. It’s an invasive and costly response, and, in 80 percent of cases, unnecessary. But a new study published today in Science Translational Medicine suggests that a blood test could save countless patients from the trauma of surgery. The report discusses a 13-blood-biomarker panel that may help identify lung nodules that are benign.
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New Principle of Chemo-Resistance Sheds Light on Evasiveness of Cancer Cells
Each year more than half a million people in the U.S. die of cancer – the major disease group that has seen the least improvement in cure rate in the past decades. Why is cancer so difficult to treat and why do almost all treatments, however new and sophisticated, almost inevitably fail after an initial success in shrinking the primary tumor?
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ISB Analysis May Lead to Earlier Diagnoses of Deadly Brain Tumor
ISB researchers present a computational analysis of astrocytoma tumors — including the most aggressive form called glioblastoma multiforme or GBM — that could enable better tumor characterization and classification. Having these data may lead to earlier diagnoses, which are crucial to enable more effective therapy choices for battling these tumors.
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Largest Genetics Catalog of Deadliest Brain Tumor Released
Glioblastoma multiforme (GBM) is the most common and deadliest of malignant primary brain tumors in adults. Because of its lethality, GBM was selected as the first brain tumor to be sequenced as part of The Cancer Genome Atlas (TCGA), a comprehensive project funded by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) to map the genomes of more than 25 types of cancer. Institute for Systems Biology (ISB) is among seven data analysis centers participating in TCGA.
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New Predictive Model for Gene Regulation of Methanogenesis of M. maripaludis
Methanogens catalyze the critical, methane-producing step (called methanogenesis) in the anaerobic decomposition of organic matter. Scientists at ISB and University of Washington led a multi-institutional effort to generate the first predictive model for gene regulation of methanogenesis in a hydrogenotrophic methanogen, Methanococcus maripaludis. The research was published on Oct. 2, 2013, in the journal Genome Research. Most species of methanogens are hydrogenotrophic –meaning they use electrons from hydrogen gas (H2) to convert carbon dioxide to methane.
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Non-Darwinian Dynamics in Therapy-Induced Cancer Drug Resistance
The development of drug resistance, the prime cause of failure in cancer therapy, is commonly explained by the selection of resistant mutant cancer cells. However, dynamic non-genetic heterogeneity of clonal cell populations continuously produces metastable phenotypic variants (persisters), some of which represent stem-like states that confer resistance.
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Pan-Cancer Project
The Cancer Genome Atlas research network has launched the Pan-Cancer project to analyze multiple tumor types together to find common events across different tumors. The availability of large cohorts and multiple different types of data at the DNA, RNA, and protein levels has made the Pan-Cancer project possible.
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Version 6 of Consensus Yeast Metabolic Network Released
Updates to maintain a state-of-the art reconstruction of the yeast metabolic network are essential to reflect our understanding of yeast metabolism and functional organization, to eliminate any inaccuracies identified in earlier iterations, to improve predictive accuracy and to continue to expand into novel subsystems to extend the comprehensiveness of the model. Here, we present version 6 of the consensus yeast metabolic network (Yeast 6) as an update to the community effort to computationally reconstruct the genome-scale metabolic network of Saccharomyces cerevisiae S288c.
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Evaluating Effects of Variable Single-Cell Protein Expression on Metabolism
Stochastic gene expression can lead to phenotypic differences among cells even in isogenic populations growing under macroscopically identical conditions. Here, we apply flux balance analysis in investigating the effects of single-cell proteomics data on the metabolic behavior of an in silico Escherichia coli population. We use the latest metabolic reconstruction integrated with transcriptional regulatory data to model realistic cells growing in a glucose minimal medium under aerobic conditions.
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New Open-Access Software Helps Predict Cellular Actions Tied to Diseases, Drug Targets
All living things are made of cells that contain DNA, which help determine their physical characteristics. In addition to this encoded genetic information, organisms are also defined by the way they decode information from interactions with their environments. Signals from the environment are interpreted by cells through a series of steps that turn proteins on or off, making up what is often referred to as the “signaling network.”
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Some Algae Are Destined to Die for the Good of the Planet
Nearly 25 gigatons of carbon is cycled annually through the oceans, replenishing resources for a healthy planet. This process is carried out by interactions among different groups of microorganisms, each performing a different role in a network that has come to be known as the microbial loop. In a study published in the journal PLOS One, researchers at the Institute for Systems Biology report the discovery that programmed cell death of algae is potentially an important step in the microbial loop.
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Unlocking Molecular Signatures of Endometrial Cancer Subtypes
Endometrial cancers affect many women in the United States. In 2012, 47,000 new cases and 8,000 deaths were estimated – making endometrial cancer the fourth most common type of cancer among US women. Accurate diagnosis of endometrial tumors is critical for doctors to determine the best treatment regimen. It turns out, however, that there are major differences between endometrial cancers — differences lurking at the molecular level. Researchers at ISB in collaboration with scientists at MD Anderson and the NIH-sponsored The Cancer Genome Atlas (TCGA) recently unlocked some of these molecular signatures, potentially allowing doctors to better distinguish aggressive cases from those that are more benign.
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Discovery of Microbial Biological Clock May Shed Light on Ocean Health
Oceans contain innumerable species of diatom microbes that are responsible for half of the Earth’s oxygen production, as well as CO2 removal, a critical exchange in the web of life. The current understanding of these single-celled organisms is limited. But researchers at the Institute for Systems Biology (ISB) and the University of Washington have made a discovery that offers new insight about the daily life cycle of the diatom, which may lead to a better understanding of ocean health in response to ocean acidification and climate change, and potential applications for biofuel production.
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Biggest Family Tree of Human Cells May Help Develop Cell-Replacement Therapies
Scientists at Institute for Systems Biology (ISB), University of Luxembourg, and Tampere University of Technology have created a method that identifies the genetic toggle switches that determine a cell’s developmental fate. This research, published on April 21 in the journal Nature Methods, may lead to new discoveries in disease treatments and tissue-regeneration technologies.
“In this elegant work, the authors propose a new way to identify genetic factors that influence cell fate based on the analysis of gene regulatory networks,” said Paul Brazhnik, PhD, of the National Institutes of Health’s National Institute of General Medical Sciences, which partly funded the work.
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Adaptor MAVS Promotes NLRP3 Mitochondrial Localization and Inflammasome Activation
NLRP3 is a key component of the macromolecular signaling complex called the inflammasome that promotes caspase 1-dependent production of IL-1β. The adaptor ASC is necessary for NLRP3-dependent inflammasome function, but it is not known whether ASC is a sufficient partner and whether inflammasome formation occurs in the cytosol or in association with mitochondria is controversial. Here, we show that the mitochondria-associated adaptor molecule, MAVS, is required for optimal NLRP3 inflammasome activity.
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Role of Key Nuclear Pore Proteins on the Assembly of Chromatin
The three-dimensional architecture of a cell’s nucleus, which contains its genetic information, is critical to determining which of a cell’s genes are actually expressed. Using systems and cell biology techniques, researchers have identified how nuclear pore complexes—collections of proteins studding the nuclear membrane— serve as key elements in defining nuclear architecture and controlling which genes get expressed. This new insight into the behavior of nuclear pore complex proteins frequently targeted by infectious diseases is published in the Feb. 28 issue of the journal Cell, which is among the top-five most prestigious journals in the country.
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A ‘Google Map’ of Human Metabolism
ISB’s Nathan Price and Vangelis Simeonidis, a visiting scholar from Luxembourg Centre for Systems Biomedicine (LCSB is a major strategic partner with ISB), contributed to this paper – “A community-driven global reconstruction of human metabolism” – that was published today in Nature Biotechnology. An excerpt describing the collaborative project from a press release is below. An interactive map is forthcoming.
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Only at ISB: Our Proteomics Journey
ISB was founded in 2000 by Dr. Lee Hood, a systems biologist; Dr. Alan Aderem, an immunologist; and Dr. Ruedi Aebersold (pictured below), a protein chemist. This dream team created a dynamic intersection of disciplines that pervades ISB today and continues to drive innovation in research, computation and technology.
