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Tag: Bioinformatics

What is new in FungiDB: a web-based bioinformatics platform for omics-scale data analysis for fungal and oomycete species

New data in FungiDB since FungiDB Release 37.
New data in FungiDB since FungiDB Release 37.

 

FungiDB (https://fungidb.org) serves as a valuable online resource that seamlessly integrates genomic and related large-scale data for a wide range of fungal and oomycete species. As an integral part of the VEuPathDB Bioinformatics Resource Center (https://veupathdb.org), FungiDB continually integrates both published and unpublished data addressing various aspects of fungal biology. Established in early 2011, the database has evolved to support 674 datasets. The datasets include over 300 genomes spanning various taxa (e.g. Ascomycota, Basidiomycota, Blastocladiomycota, Chytridiomycota, Mucoromycota, as well as Albuginales, Peronosporales, Pythiales, and Saprolegniales). In addition to genomic assemblies and annotation, over 300 extra datasets encompassing diverse information, such as expression and variation data, are also available. The resource also provides an intuitive web-based interface, facilitating comprehensive approaches to data mining and visualization. Users can test their hypotheses and navigate through omics-scale datasets using a built-in search strategy system. Moreover, FungiDB offers capabilities for private data analysis via the integrated VEuPathDB Galaxy platform. FungiDB also permits genome improvements by capturing expert knowledge through the User Comments system and the Apollo genome annotation editor for structural and functional gene curation. FungiDB facilitates data exploration and analysis and contributes to advancing research efforts by capturing expert knowledge for fungal and oomycete species.

Evelina Y Basenko, Achchuthan Shanmugasundram, Ulrike Böhme, David Starns, Paul A Wilkinson, Helen R Davison, Kathryn Crouch, Gareth Maslen, Omar S Harb, Beatrice Amos, Mary Ann McDowell, Jessica C Kissinger, David S Roos, Andrew Jones. Genetics. 2024 Mar 26:iyae035. doi: 10.1093/genetics/iyae035

TriTrypDB: An integrated functional genomics resource for kinetoplastida

Parasitic diseases caused by kinetoplastid parasites are a burden to public health throughout tropical and subtropical regions of the world. TriTrypDB (https://tritrypdb.org) is a free online resource for data mining of genomic and functional data from these kinetoplastid parasites and is part of the VEuPathDB Bioinformatics Resource Center (https://veupathdb.org). As of release 59, TriTrypDB hosts 83 kinetoplastid genomes, nine of which, including Trypanosoma brucei brucei TREU927, Trypanosoma cruzi CL Brener and Leishmania major Friedlin, undergo manual curation by integrating information from scientific publications, high-throughput assays and user submitted comments. TriTrypDB also integrates transcriptomic, proteomic, epigenomic, population-level and isolate data, functional information from genome-wide RNAi knock-down and fluorescent tagging, and results from automated bioinformatics analysis pipelines. TriTrypDB offers a user-friendly web interface embedded with a genome browser, search strategy system and bioinformatics tools to support custom in silico experiments that leverage integrated data. A Galaxy workspace enables users to analyze their private data (e.g., RNA-sequencing, variant calling, etc.) and explore their results privately in the context of publicly available information in the database. The recent addition of an annotation platform based on Apollo enables users to provide both functional and structural changes that will appear as ‘community annotations’ immediately and, pending curatorial review, will be integrated into the official genome annotation.

Achchuthan Shanmugasundram, David Starns, Ulrike Böhme, Beatrice Amos, Paul A Wilkinson, Omar S Harb, Susanne Warrenfeltz, Jessica C Kissinger, Mary Ann McDowell, David S Roos, Kathryn Crouch, Andrew R Jones. PLoS Negl Trop Dis. 2023 Jan 19;17(1):e0011058. doi: 10.1371/journal.pntd.0011058.

Sharing the Knowledge: NIH Award Supports Expanded Genomics Data Resource

By: Alan Flurry

A team led by scientists at the University of Pennsylvania and University of Georgia provides thousands of researchers around the world with access to the Eukaryotic Pathogen Genomics Database (EuPathDB.org), a collection of resources for analyzing large-scale datasets associated with microbial pathogens. These include the parasites responsible for malaria, sleeping sickness, and toxoplasmosis; the fungi responsible for thrush, aspergillosis and Valley Fever; and many other important diseases. In parallel, a team led by investigators at the University of Notre Dame has been responsible for similar resources covering invertebrate vectors of disease (VectorBase.org), including the mosquitoes transmitting malaria, Zika, and yellow fever, the ticks responsible for Lyme disease and Rocky Mountain Spotted Fever, and others.

To ensure that this important work continues, the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health, has awarded a new contract to integrate these resources, worth up to $7.2 million in 2019-2020. The five‐year award for this project, rebranded as VEuPathDB.org (The Eukaryotic Pathogen, Host & Vector Genomics Resource) could total as much as $38.4 million if all associated options are exercised.

The patterns revealed by such “Big Data” provide insight into important diseases, permit the development of diagnostic methods, and define drug and vaccine targets. But to be useful, these immense datasets must be sensibly organized and made conveniently accessible to the researchers worldwide. The integrated VEuPathDB database hosts data on thousands of genomes, representing hundreds of species, along with extensive information on isolate provenance, gene function and the like.

The award is based at Penn, and directed by David S Roos, E Otis Kendall Professor of Biology in the School of Arts & Sciences. Key subcontracts include the University of Georgia (Joint PI Jessica C. Kissinger, Distinguished Professor of Genetics and Bioinformatics in the Franklin College of Arts and Sciences and the Center for Tropical and Emerging Global Diseases), University of Notre Dame (Joint PI Mary Ann McDowell, Associate Professor of Biological Sciences at the Eck Institute for Global Health).  Additional co-investigators include Professors Christian Stoeckert of Penn’s Perelman School of Medicine, Mark Caddick of the University of Liverpool, George K Christophides of Imperial College London, and Paul Flicek, Associate Director of the EMBL-EBI (European Bioinformatics Institute).

“It is wonderful to see the continued investment by NIH, the Wellcome Trust and others in resources that make performing much needed global research on infectious diseases both easier and better,” Kissinger said. “Datasets are larger and more complex than ever due to significant advances in technology. These breakthroughs create challenges for making the resulting data truly accessible and usable by the average researcher.  We strive to remove barriers, integrate diverse data and accelerate the speed with which new hypotheses can be generated and ideas tested both in silico and in the lab.”

“A critical aspect of this now joint program will be its accessibility throughout the world, empowering any infectious disease investigator to interrogate these highly complex databases in comprehensible and productive ways,” said Dan Colley, UGA professor of microbiology and member of the CTEGD who has conducted extensive research on n schistosomiasis in western Kenya. “These databases have led, and the merged data base will lead, to the design of new drugs and studies on how to better control and eliminate these major public health challenges, such as malaria, toxoplasmosis, yellow fever, eastern equine encephalitis and Lyme disease.”

“Since its conception, corresponding with the release of the first parasite genomes, EuPathDB has been a transformative tool in our search for a better understanding of human disease and parasite biology,” said Stephen Hadjuk, Professor Emeritus of biochemistry & molecular biology at UGA whose lab investigates trypanosomes, the causative agent of an human African sleeping sickness. “Today, it’s difficult to imagine any serious research on parasites and host pathology that doesn’t rely, at least to some extent, on EuPathDB. The decision to incorporate the vectors database into the eukaryotic pathogens database was brilliant, and makes this is an exciting new chapter in the EuPathDB story.”

“Innumerable investigators, including my own laboratory, rely on daily access to the high quality genomic and functional datasets made available by the VEuPathDB Project,” says Keith Gull, Professor of Molecular Microbiology at Oxford University.  “Sustainable support for such resources is imperative if we are to capitalize on the promise of modern technologies for scientific discovery and translational application.”  Joe Heitman, James B Duke Professor / Chair of Molecular Genetics & Microbiology at Duke University agrees: “Inclusion of fungal pathogens under the BRC umbrella has greatly enhanced our ability to study important human mycoses.  Cross-species comparisons provide insights into the biology and pathogenesis of these fascinating organisms, which can be deadly – but can also serve as workhorses for valuable biotechnology development.”

Originally published at https://www.franklin.uga.edu/news/stories/2019/sharing-knowledge-nih-award-supports-expanded-genomics-data-resource

Building on big data, UPenn and UGA awarded $23.4 million pathogen genomics database contract

Jessica Kissinger

Athens, Ga. – A genome database team led by University of Pennsylvania and University of Georgia scientists has been awarded a new contract from the National Institutes of Allergy and Infectious Disease worth $4.3 million in 2014-2015. Assuming annual renewal, this five-year award is expected to total $23.4 million.

The team has been responsible for developing genome database resources for microbial pathogens, including the parasites responsible for malaria, sleeping sickness, toxoplasmosis and many other important diseases.

The new contract ensures work will continue on the Eukaryotic Pathogen Genomics Database—known as EuPathDB—to provide the global scientific community with free access to a wealth of genomic data related to microbial pathogens important to human health and biosecurity. EuPathDB expedites biomedical research in the lab, field and clinic, enabling the development of innovative diagnostics, therapies and vaccines.

Each month, EuPathDB receives over 6.5 million hits from 13,000 unique visitors in more than 100 countries, including areas where tropical diseases such as malaria are endemic. India is now the second largest user of its plasmodium genome database, and over 5 percent of users hail from Africa. The overall project employs 28 people on four continents.

EuPathDB is jointly directed by principal investigators David S. Roos, the E. Otis Kendall Professor of Biology in Penn’s School of Arts and Sciences, and Jessica C. Kissinger, professor of genetics and director of the UGA Institute of Bioinformatics. Christian Stoeckert of Penn’s Perelman School of Medicine is a co-investigator.

One of four pathogen bioinformatics resource centers supported by the National Institutes of Health, EuPathDB is responsible for disease-causing eukaryotes, which are organisms that possess a membrane-bound nucleus. Other centers support data on viruses, bacteria and insect vectors of disease.

“This database has expedited research in many ways,” said Kissinger, a member of the UGA Center for Tropical and Emerging Global Diseases. “Vaccine scientists frequently want to examine how proteins have changed over time to identify those with signatures indicating that they provoke the human immune system. Those studying a specific antigen may wish to examine its structure and diversity in order to prioritize those regions that might be most promising and relatively unlikely to develop resistance.”

Since its prototype was launched in 1999, the EuPathDB family of databases has become increasingly complex and increasingly valuable as a resource for researchers around the world. In total, the databases comprise about 9 terabytes of data and have been cited more than 8,000 times in the scientific literature.

“The costs and time required for genome sequencing have plummeted in the past 10 years thanks to advances in technology,” Kissinger said. “Organizing this data, maintaining it in a way that is accessible and easy to use for researchers around the world, 24 hours a day, is our great challenge-and one that presents exciting opportunities for funders and other philanthropic organizations that support pathogen research.”

The latest contract is the third time that NIH has awarded support to EuPathDB, building on previous contracts issued in 2004 and 2009 as well as prior grant funding from the NIH and the Burroughs Wellcome Fund. Affiliated projects have also been supported by the Wellcome Trust, the Bill and Melinda Gates Foundation, the Sloan Foundation, the World Health Organization, the U.S. Department of Agriculture, the Brazilian government and other organizations.

“The sophistication of the questions people can ask continues to increase,” Roos said in a press release from UPenn. “As we move to the next phase of this project, our job is to ensure that this resource remains dynamic, taking into account how people interact with the data in ways that can have a real impact on global health.”

Writer: Alan Flurry
Contact:Jessica Kissinger

UGA, Emory collaborate to leverage strengths in infectious disease research

Jessica Kissinger

Athens, Ga. – The University of Georgia and Emory University are strengthening their collaborations to elevate the position of the Atlanta-Athens corridor as a national hub for infectious disease research.

The two institutions are currently working together on grant and contract-funded projects totaling more than $45 million, including a Center of Excellence for Influenza Research and Surveillance and a malaria research consortium, both funded by the National Institutes of Health (NIH). In addition, they are developing a new diagnostic test for tuberculosis and working to create a new HIV vaccine, among other projects.

These partnerships and others like them will be enhanced by a series of ongoing meetings among senior administrators initiated by the institution’s two presidents, Jere W. Morehead of UGA and James Wagner of Emory, shortly after Morehead came into office.

“The combined research strengths of our two institutions, particularly in infectious diseases, create a formidable effort to develop better methods of prevention, detection and treatment for some of the most challenging global health challenges,” said Wagner.

“These collaborations reflect the complementary strengths of two of Georgia’s leading research universities and our shared commitment to conducting globally significant research,” said Morehead. “By working together, we are advancing the state’s economically important bioscience sector while laying the foundation for improvements in health and quality of life around the world.”

Earlier this year, the Emory-UGA Center of Excellence for Influenza Research and Surveillance (CEIRS) received a $3.6 million contract-with potential funding up to $26.7 million over seven years-from the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH. The Emory-UGA CEIRS, originally launched and funded in 2007, is one of five national centers that integrate research to lessen the impact of epidemic influenza and improve pandemic influenza preparedness.

The Emory-UGA CEIRS is led by Dr. Walter Orenstein, professor of medicine and associate director of the Emory Vaccine Center. Researchers at Emory are studying how flu viruses cause infection and spread in the population, the human immune response to flu vaccines, flu infection in pregnancy and the response to flu vaccines in pregnant women. Under the leadership of Ralph Tripp, Georgia Research Alliance Chair in Vaccine and Therapeutic Development at UGA, the center has established an extensive surveillance network to identify flu viruses in swine that could potentially become human pandemic strains and is evaluating the immune response to flu viruses and vaccines. In addition, the researchers are collaborating with colleagues in China to monitor flu viruses that infect swine and poultry.

“Through merging the research expertise of our two institutions, our influenza center is a key component of the national effort to prepare for and help prevent emerging influenza outbreaks, including seasonal flu and pandemic strains,” said Orenstein.

Emory, UGA and Georgia Tech also are collaborating within a malaria research consortium funded by a five-year contract of up to $19.4 million from the NIAID. Scientists in the Malaria Host-Pathogen Interaction Center (MaHPIC), led by Dr. Mary Galinski from the Emory School of Medicine and Yerkes National Primate Research Center, are building a “molecular encyclopedia” cataloguing how malaria parasites interact with their human and animal hosts. New mathematical models are helping analyze the details of an infection and identifying patterns that predict the course of the disease and its severity.

“New tests from our effort could help us screen for dormant parasites and identify biomarkers to predict which cases will become the most severe, potentially leading to drug discovery and a malaria vaccine,” said Galinski.

UGA professor of genetics Jessica Kissinger, who directs the UGA Institute of Bioinformatics, is leading a team that is organizing, distributing and mining the massive quantities of data produced by the project with the ultimate goal of identifying new opportunities to diagnose the disease, which causes an estimated 660,000 deaths annually.

“The goal of my team is to integrate the terabytes of data being produced on both the host and the parasite and make it accessible to our mathematical modelers, who are looking for patterns and signals, as well as the global malaria research community to guarantee that this large investment has the biggest impact possible on malaria research,” Kissinger said.

In addition to flu and malaria, UGA and Emory researchers are making strides against tuberculosis, which kills an estimated 1.5 million people worldwide each year. A team of scientists from the two institutions recently developed the first rapid diagnostic test to identify latent tuberculosis, the most common form of the disease. Latent tuberculosis doesn’t cause symptoms in people who are otherwise healthy, but it can develop into dangerous and potentially deadly tuberculosis in late-stage AIDS patients and other vulnerable populations.

The diagnostic test-developed by UGA Athletic Association Professor of Infectious Diseases Fred Quinn and Dr. Henry M. Blumberg, professor of medicine in the division of infectious diseases at the Emory School of Medicine-measures the concentration of proteins that are only present if the bacteria that cause tuberculosis are replicating. With $1 million in funding from the Food and Drug Administration, the researchers completed a small but promising preliminary study and are now wrapping up a larger study to verify the effectiveness of the diagnostic method.

“The current tests cannot identify latent disease, which may account for 60 to 90 percent of the potential two billion cases worldwide,” said Quinn, a faculty member in the UGA College of Veterinary Medicine. “With an accurate diagnosis of latent tuberculosis, patients-particularly those with compromised immune systems-can receive potentially lifesaving treatment.”

In a project funded by a five-year, $2.8 million NIH grant, Emory and UGA researchers are developing an HIV vaccine that induces the immune system to attack the virus before it can spread through the body. The vaccine uses a virus known as PIV5, which causes kennel cough in dogs but doesn’t cause symptoms in humans, and virus-like particles that mimic the HIV virus. This one-two punch vaccine approach could stimulate immune responses in areas of the body where the virus is known to first infect cells, therefore preventing further spread.

“In the past 30 years of HIV vaccine research, we have learned a lot about how to generate immune responses that might protect people from infection. However, we don’t yet have a vaccine that we know for certain will protect individuals from HIV,” said Emory Professor of Pediatrics and Microbiology Dr. Paul Spearman, who is collaborating with Biao He, the Davison Distinguished University Chair in Veterinary Medicine at UGA.

“I am delighted to be working with Dr. He, the world’s expert in the use of PIV5 as a vaccine. Together we are optimistic that this prime-boost vaccine approach will generate immune responses to combat the virus in mucosal sites such as the gut. If successful, this will prevent the very early phase of HIV spread and could protect against HIV infection and AIDS.”

Writer: Sam Fahmy
Writer: Holly Korschun