Posts Tagged ‘Gene’

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UPC teams conduct research in biomedical engineering to improve people’s health

UPC teams conduct research in biomedical engineering to improve people’s health

Systems to improve patient rehabilitation, methods that help detect diseases, and smart biomaterials for optimising treatments—scientific advances in the field of biomedical engineering are unstoppable. A number of leading UPC teams are carrying out research aimed at harnessing technology to improve people’s health.

Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s. Optimising treatment and rehabilitation of the people it affects and improving their quality of life is the goal of Joan Cabestany and Andreu Català, researchers at the Technical Research Centre for Dependency Care and Autonomous Living (CETpD) of the Universitat Politècnica de Catalunya · BarcelonaTech (UPC).

The two engineers are heading up a European project known as REMPARK (Personal Health Device for the Remote and Autonomous Management of Parkinson’s Disease), which has a budget of €4.73 million. The objective is to develop a pioneering wearable monitoring system that can be used to identify and quantify, in real time and with high reliability, the motor status of Parkinson’s patients during their everyday lives. The system will act automatically—though always under medical supervision—in response to the situations that are most incapacitating for patients, intervening in the least invasive and most effective way possible. Other participants in this ambitious project coordinated by the UPC include the Teknon Medical Centre, Telefónica R&D, the European Parkinson’s Disease Association, and a number of research centres and companies based in Germany, Portugal, Italy, Israel, Ireland, Sweden and Belgium.

The system being developed consists of two elements: a bracelet equipped with a sensor for measuring tremor in patients and a smart device the size of a mobile phone, which is worn at the waist on a belt made of biocompatible material. The device is equipped with a set of sensors and has the capacity to process and wirelessly transmit all the information collected and processed.

When a gait-freezing episode occurs, the REMPARK system will act to synchronise the patient’s movements. This will be achieved by means of auditory, visual or haptic (touch-related) cueing devices, a pump for regulated subcutaneous drug delivery, and a functional electrical stimulation (FES) system. “The device will make it possible to quantify the effects of a drug in a particular patient and adjust the dose accordingly,” says Joan Cabestany, stressing that REMPARK is “a personalised system that adapts to each person’s needs.”

For the first time in Europe, REMPARK will be tested on a hundred patients in their homes. “We want to use the technology to give Parkinson’s patients back their confidence, which is gradually eroded by the disease,” says Andreu Català. The project “will reduce the number of hospitalisations and improve patient treatment and rehabilitation,” adds the researcher, who works at the Vilanova i la Geltrú Campus.

Stress-free cells

The REMPARK project is set to run until 2015, but others are yielding results that are about to hit the market. This was clear at the BIO International Convention, the world’s largest biotechnology exhibition, which was held in Boston (Massachusetts, United States) last June.

The UPC presented a number of patents at the event, including an automatic method for introducing substances such as drugs and DNA into cells (transfection). The method, known as in vitro electroporation, is more efficient and economical than existing approaches.

The technique, which is applied manually, is commonly used in gene therapy, cell-based therapies, and tumour treatment by electrochemotherapy. Cells are detached from the bottom of the plates where they are grown and put into suspension, i.e. into a mixture. They are then placed in a special cuvette with aluminium electrodes on its sides. The cuvette is loaded into a device (an electroporator) that creates a high-intensity electric field across the cells, causing the pores in the cell membrane to open. Substances can then be introduced through these pores.

The new system simplifies and automates this process. A microelectrode assembly is introduced directly into the culture plate and placed at a distance of 10 ìm (10 millionths of a metre) from the cells. A 20 V electric field is then applied (in the conventional process a 500 V field is used). The lower voltage reduces the cost of the devices used to carry out these biotechnological processes and subjects the cells to less stress. The low cost of the microelectrodes also makes it possible to produce single-use electroporators. This patent was developed by researcher Ramon Bragós and doctoral student Tomàs Garcia, who are attached to the Biomedical Engineering Research Centre (CREB), in collaboration with a team at the University of Barcelona (UB).

The UPC is also contributing to major advances in the development of medical devices and diagnostic imaging. The UPC’s Institute of Industrial and Control Engineering (IOC) and the Pulmonology Research Group of Bellvitge Hospital’s Institute for Biomedical Research have developed a virtual bronchoscopy system that improves the diagnosis of lung cancer. The technology provides doctors with information that enables them to decide with more confidence whether an actual bronchoscopy is necessary or not. This helps minimise risk and discomfort for patients.

The system is based on images provided by a virtual bronchoscopy using 2D computed tomography images. The novel feature of the system is that it takes into account the geometry and kinematic constraints of the bronchoscope.

The device is designed so that a pulmonologist can virtually navigate through a patient’s airways and simulate the movements that will later be executed when a flexible bronchoscope is used to perform the examination. It is a useful tool that facilitates “very realistic planning of the most feasible path from the trachea to peripheral pulmonary lesions,” says Jan Rosell, the researcher who carried out the project together with Paolo Cabras and Alexander Pérez, who also work with the IOC. “Doctors can also use the device to determine whether the end of the bronchoscope will reach a lesion, or, if not, how close it can be manoeuvred and what technique will need to be used to obtain a biopsy sample,” Rosell adds.

In addition to pursuing advances in diagnostic imaging, molecular biology and telemedicine, UPC researchers are also doing innovative work in another area of interest: metabolomics, the scientific study of chemical processes involving metabolites. It is in this field that another CREB team has patented an innovative software tool. The advanced program, based on a new algorithm, helps medical professionals make more accurate, automated predictions in disease diagnosis and drug screening.

Developed by Àlex Perera and Francesc Fernández in collaboration with researchers with the University of Barcelona’s Department of Nutrition and Food Science, the tool improves detection of biomarkers, the biological markers used to detect diseases.

Another advantage of the software is that it reduces prediction error in metabolomic analysis and testing (used to examine the small organic molecules in biological systems). Metabolomic analyses are based on biological samples of urine or blood, nuclear magnetic resonance (NMR) techniques, and mass spectrometry (LC/MS). Making predictions in this area is complex because it requires analysis of extensive data obtained from individual samples, but it is of vital importance in evaluating the effectiveness of new drugs, for example.

New test for tuberculosis

Tuberculosis is one of the diseases that accounts for the most morbidity and mortality worldwide. Despite this, there are still a lot of unanswered questions about the disease and many scientific challenges remain to be tackled. Daniel López Codina and Clara Prats of the UPC’s Discrete Modelling and Simulation of Biological Systems group have carried out research in this field in collaboration with a team at the Experimental Tuberculosis Unit of the Germans Trias i Pujol Health Sciences Research Institute Foundation.

The two teams have patented a new method that offers a fast, easy and reliable way to determine the virulence (ability to produce disease) of Koch’s bacillus. The technique allows specialists to make more accurate diagnoses.

López Codina’s team observed the tuberculosis bacillus (Mycobacterium tuberculosis) in an in vitro culture and looked at the way it grows by forming clumps. Given the difficulty of applying conventional microbiological methods with this type of culture, the researchers used an alternative approach: microscopy and analysis with image processing techniques. “This is the first time we’ve been able to use a culture to observe two different strains of the bacterial parasite and the existence of a correlation between the characteristic clumping pattern and the virulence of the disease,” said the researcher.

The results have created a new business opportunity for companies involved in biomedical imaging and diagnostic testing.

Projects like these highlight the huge potential of engineering and medicine to continue delivering solutions that improve people’s quality of life.

Source : http://www.news-medical.net/news/20121123/UPC-teams-conduct-research-in-biomedical-engineering-to-improve-peoples-health.aspx

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UPC teams conduct research in biomedical engineering to improve people’s health

UPC teams conduct research in biomedical engineering to improve people’s health

Systems to improve patient rehabilitation, methods that help detect diseases, and smart biomaterials for optimising treatments—scientific advances in the field of biomedical engineering are unstoppable. A number of leading UPC teams are carrying out research aimed at harnessing technology to improve people’s health.

Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s. Optimising treatment and rehabilitation of the people it affects and improving their quality of life is the goal of Joan Cabestany and Andreu Català, researchers at the Technical Research Centre for Dependency Care and Autonomous Living (CETpD) of the Universitat Politècnica de Catalunya · BarcelonaTech (UPC).

The two engineers are heading up a European project known as REMPARK (Personal Health Device for the Remote and Autonomous Management of Parkinson’s Disease), which has a budget of €4.73 million. The objective is to develop a pioneering wearable monitoring system that can be used to identify and quantify, in real time and with high reliability, the motor status of Parkinson’s patients during their everyday lives. The system will act automatically—though always under medical supervision—in response to the situations that are most incapacitating for patients, intervening in the least invasive and most effective way possible. Other participants in this ambitious project coordinated by the UPC include the Teknon Medical Centre, Telefónica R&D, the European Parkinson’s Disease Association, and a number of research centres and companies based in Germany, Portugal, Italy, Israel, Ireland, Sweden and Belgium.

The system being developed consists of two elements: a bracelet equipped with a sensor for measuring tremor in patients and a smart device the size of a mobile phone, which is worn at the waist on a belt made of biocompatible material. The device is equipped with a set of sensors and has the capacity to process and wirelessly transmit all the information collected and processed.

When a gait-freezing episode occurs, the REMPARK system will act to synchronise the patient’s movements. This will be achieved by means of auditory, visual or haptic (touch-related) cueing devices, a pump for regulated subcutaneous drug delivery, and a functional electrical stimulation (FES) system. “The device will make it possible to quantify the effects of a drug in a particular patient and adjust the dose accordingly,” says Joan Cabestany, stressing that REMPARK is “a personalised system that adapts to each person’s needs.”

For the first time in Europe, REMPARK will be tested on a hundred patients in their homes. “We want to use the technology to give Parkinson’s patients back their confidence, which is gradually eroded by the disease,” says Andreu Català. The project “will reduce the number of hospitalisations and improve patient treatment and rehabilitation,” adds the researcher, who works at the Vilanova i la Geltrú Campus.

Stress-free cells

The REMPARK project is set to run until 2015, but others are yielding results that are about to hit the market. This was clear at the BIO International Convention, the world’s largest biotechnology exhibition, which was held in Boston (Massachusetts, United States) last June.

The UPC presented a number of patents at the event, including an automatic method for introducing substances such as drugs and DNA into cells (transfection). The method, known as in vitro electroporation, is more efficient and economical than existing approaches.

The technique, which is applied manually, is commonly used in gene therapy, cell-based therapies, and tumour treatment by electrochemotherapy. Cells are detached from the bottom of the plates where they are grown and put into suspension, i.e. into a mixture. They are then placed in a special cuvette with aluminium electrodes on its sides. The cuvette is loaded into a device (an electroporator) that creates a high-intensity electric field across the cells, causing the pores in the cell membrane to open. Substances can then be introduced through these pores.

The new system simplifies and automates this process. A microelectrode assembly is introduced directly into the culture plate and placed at a distance of 10 ìm (10 millionths of a metre) from the cells. A 20 V electric field is then applied (in the conventional process a 500 V field is used). The lower voltage reduces the cost of the devices used to carry out these biotechnological processes and subjects the cells to less stress. The low cost of the microelectrodes also makes it possible to produce single-use electroporators. This patent was developed by researcher Ramon Bragós and doctoral student Tomàs Garcia, who are attached to the Biomedical Engineering Research Centre (CREB), in collaboration with a team at the University of Barcelona (UB).

The UPC is also contributing to major advances in the development of medical devices and diagnostic imaging. The UPC’s Institute of Industrial and Control Engineering (IOC) and the Pulmonology Research Group of Bellvitge Hospital’s Institute for Biomedical Research have developed a virtual bronchoscopy system that improves the diagnosis of lung cancer. The technology provides doctors with information that enables them to decide with more confidence whether an actual bronchoscopy is necessary or not. This helps minimise risk and discomfort for patients.

The system is based on images provided by a virtual bronchoscopy using 2D computed tomography images. The novel feature of the system is that it takes into account the geometry and kinematic constraints of the bronchoscope.

The device is designed so that a pulmonologist can virtually navigate through a patient’s airways and simulate the movements that will later be executed when a flexible bronchoscope is used to perform the examination. It is a useful tool that facilitates “very realistic planning of the most feasible path from the trachea to peripheral pulmonary lesions,” says Jan Rosell, the researcher who carried out the project together with Paolo Cabras and Alexander Pérez, who also work with the IOC. “Doctors can also use the device to determine whether the end of the bronchoscope will reach a lesion, or, if not, how close it can be manoeuvred and what technique will need to be used to obtain a biopsy sample,” Rosell adds.

In addition to pursuing advances in diagnostic imaging, molecular biology and telemedicine, UPC researchers are also doing innovative work in another area of interest: metabolomics, the scientific study of chemical processes involving metabolites. It is in this field that another CREB team has patented an innovative software tool. The advanced program, based on a new algorithm, helps medical professionals make more accurate, automated predictions in disease diagnosis and drug screening.

Developed by Àlex Perera and Francesc Fernández in collaboration with researchers with the University of Barcelona’s Department of Nutrition and Food Science, the tool improves detection of biomarkers, the biological markers used to detect diseases.

Another advantage of the software is that it reduces prediction error in metabolomic analysis and testing (used to examine the small organic molecules in biological systems). Metabolomic analyses are based on biological samples of urine or blood, nuclear magnetic resonance (NMR) techniques, and mass spectrometry (LC/MS). Making predictions in this area is complex because it requires analysis of extensive data obtained from individual samples, but it is of vital importance in evaluating the effectiveness of new drugs, for example.

New test for tuberculosis

Tuberculosis is one of the diseases that accounts for the most morbidity and mortality worldwide. Despite this, there are still a lot of unanswered questions about the disease and many scientific challenges remain to be tackled. Daniel López Codina and Clara Prats of the UPC’s Discrete Modelling and Simulation of Biological Systems group have carried out research in this field in collaboration with a team at the Experimental Tuberculosis Unit of the Germans Trias i Pujol Health Sciences Research Institute Foundation.

The two teams have patented a new method that offers a fast, easy and reliable way to determine the virulence (ability to produce disease) of Koch’s bacillus. The technique allows specialists to make more accurate diagnoses.

López Codina’s team observed the tuberculosis bacillus (Mycobacterium tuberculosis) in an in vitro culture and looked at the way it grows by forming clumps. Given the difficulty of applying conventional microbiological methods with this type of culture, the researchers used an alternative approach: microscopy and analysis with image processing techniques. “This is the first time we’ve been able to use a culture to observe two different strains of the bacterial parasite and the existence of a correlation between the characteristic clumping pattern and the virulence of the disease,” said the researcher.

The results have created a new business opportunity for companies involved in biomedical imaging and diagnostic testing.

Projects like these highlight the huge potential of engineering and medicine to continue delivering solutions that improve people’s quality of life.

Source : http://www.news-medical.net/news/20121123/UPC-teams-conduct-research-in-biomedical-engineering-to-improve-peoples-health.aspx

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EMUC discusses current and future prospects in imaging for prostate cancer

EMUC discusses current and future prospects in imaging for prostate cancer

At the 4th European Multidisciplinary Meeting on Urological Cancers (EMUC) held this weekend in Barcelona, Spain, specialists from radiology, urology, medical oncology and pathology said that new developments and research are already underway but benefits to patients would take some time due to the need for clinical trials, the high cost of funding research and the ability of cancer experts to efficiently take advantage of new insights and approaches, among other challenges.

“The future of imaging for prostate cancer has already begun,” said radiologist G. Villeirs (BE) in his overview lecture on current and future prospects in imaging for prostate cancer. Villeirs enumerated several technologies that can provide or improve current imaging techniques such as T2 Weighted MRI (Magnetic Resonance Imaging), Diffusion-Weighted Imaging, Dynamic Contrast-Enhanced MRI, Magnetic Resonance (MR) spectroscopy and Multiparametric MRI.

Many of these techniques have been undergoing research tests and refinements, according to Villeirs as he added that it would be a matter of time when the optimal use of these techniques will provide uro-oncological experts the benefits of more accurate, insightful diagnoses.

“In dynamic contrast-enhanced MRI, its most important use is in detection and localisation (of prostate tumours), with an accuracy of up to 90%,” he said.

M. Rubin (USA) spoke on the research developments in biomarkers and noted that diseases like castration resistant prostate cancer (CRPC), for instance, remains a challenge to researchers due to its heterogenous nature. He mentioned that the next generation of PCa biomarkers are urine-based assays (which detects early aggressive PCa), and tissue/CTC-based assays which are employed for prediction and precision medicine.

Urine-based assays include PCA3 (already FDA-approved), TMPRSS2-ERG (in development), other fusions (in development) and SPOP/CHD1 (early discovery), while tissue-based assays include androgen receptor gene (AR), BRCA2 and AURKA. Rubin said that TMPRSS2-ERG which has a specificity of 97% and sensitivity of 96% is commercially available for clinical use in the US and Europe.

The unmet biomarker needs for PCa, according to Rubin, should address the following aims: to distinguish BPH from prostate cancer, to detect the aggressive forms from the indolent cases and to identify the metastatic cancer predictors.

Meanwhile, urologist A. Briganti (IT) gave a comprehensive update on the future of surgery for prostate cancer and his expectations in the coming years. “We need to perform the correct surgery – in the right patient – to decrease the need for secondary therapies,” said Briganti, adding that identifying the right patient for the correct surgery is “…key in optimizing the future of surgery.”

He explained that correctly prescribed surgery will have the higher chance of cure only “…if combined with adjuvant therapy and delivered only to those patients who really deserve it.” He also expects that minimally invasive approaches will change the toxicity profile of more extensive surgical approaches.

“But data are still lacking,” Briganti noted.

M. Van Vulpen (NL) presented the radiation oncologist viewpoint regarding external beam radiotherapy and brachytherapy, while J. De Bono (UK) took up the topic of future medical therapies in prostate cancer.

Van Vulpen also expressed confidence that radiotherapy will remain in the forefront of new developments as he noted several breakthrough developments such as CT-linac (linear accelerator) which is used when prostate movements are problematic for intensity-modulated radiotherapy. He also mentioned computerised tumour detection which can localise tumour and show its aggressiveness.

De Bono gave a thorough overview on medical therapies, stressing that cancer experts should aim to decrease over diagnosis of benign PCa and the over treatment of ‘benign’ disease. De Bono noted that to improve therapeutic options doctors need to cure more high-risk/intermediate disease and improve the outcome from metastatic PCa.

He explained that three elements are important in improving treatment outcomes, namely an improved biological understanding of PCa, developing deliverable biomarkers that can be used for precision medicine, and by developing new drugs through hypotheses testing and are biomarker-driven.

Source : http://www.news-medical.net/news/20121119/EMUC-discusses-current-and-future-prospects-in-imaging-for-prostate-cancer.aspx

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New England Biolabs launches new NEBNext Ultra kits at ASHG annual meeting

New England Biolabs launches new NEBNext Ultra kits at ASHG annual meeting

New England Biolabs, Inc. (NEB) launched their new NEBNext® “Ultra” kits at the recent American Society for Human Genetics (ASHG) annual meeting. These kits provide streamlined, low-input methods to prepare DNA and RNA libraries for Illumina® next generation sequencing. The supplied protocols and reagents are designed to maximize useful data from a broad range of samples, including those available in limited amounts.

The NEBNext Ultra DNA and Ultra RNA Library Kits produce high-yield libraries from 5 ng to 1 ug of input DNA, or as little as 10 ng of input RNA. The input RNA can be total RNA, purified mRNA or rRNA-depleted RNA.

Early access user Cynthia Hendrickson, Ph.D., at the HudsonAlpha Institute for Biotechnology, reports that in initial experiments, NEB’s new method “has allowed us to reduce our DNA inputs for exome enrichment from micrograms to a few hundred nanograms, while providing a simpler, faster protocol that minimizes the amount of hands-on time required.”

Another early access user, Momchilo Vuyisich, Ph.D., at the Los Alamos National Laboratory, says, “After testing several NGS library prep kits, we have found that the NEBNext Ultra DNA kit for Illumina has the best overall utility for resequencing and assembly of bacterial genomes. The kit offers an unmatched combination of ease-of-use, low cost, robustness and low input DNA requirements. It consistently produces excellent sequencing data.”

The new Ultra kits contain novel ligation reagents, as well as NEB’s NEBNext NGS-optimized formulation of Q5® High-Fidelity DNA polymerase, which provides ultra high-fidelity amplification and minimized GC bias.

NEB’s streamlined protocol for constructing DNA libraries with the Ultra kit requires only 15 minutes of hands-on-time, and is complete in 2.5 hours. The Ultra RNA workflow also incorporates a streamlined protocol; the workflow is complete in 4-5 hours, with only 30 minutes of hands-on time.

Source : http://www.news-medical.net/news/20121117/New-England-Biolabs-launches-new-NEBNext-Ultra-kits-at-ASHG-annual-meeting.aspx

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Researchers sequence the DNA of 6,700 exomes of cystic fibrosis patients

Researchers sequence the DNA of 6,700 exomes of cystic fibrosis patients

A multi-institutional team of researchers has sequenced the DNA of 6,700 exomes, the portion of the genome that contains protein-coding genes, as part of the National Heart, Lung and Blood Institute (NHLBI)-funded Exome Sequencing Project, one of the largest medical sequencing studies ever undertaken.

Scientists participating in the project initially expected that individual rare variants would have a greater effect on over 80 heart, lung and blood related traits and diseases of high public health significance, said Suzanne M. Leal, Ph.D., professor and director, Center for Statistical Genetics in the Department of Molecular and Human Genetics of Baylor College of Medicine in Houston, TX.

The researchers found that many (1.1 million) of the 1.2 million coding variants that they identified in exome data from 4,420 European-Americans and 2,312 African-Americans occurred very infrequently in the population and often were only observed in a single individual, explained Dr. Leal, who presented the findings today at the American Society of Human Genetics 2012 meeting.

Dr. Leal added that most of the observed coding variants are population specific, occurring in either European or African Americans. “Of the identified variants, about 720,000 change the genetic code in a manner that could produce flawed proteins. Yet the role played by most of these variants in disease development has not been established,” she said.

The major goal of the project was to understand how variation in the exome affects heart, lung and blood related traits and diseases.

The study participants were selected from a sample of over 220,000 individuals who participated in another National Institute of Health (NIH) supported study that had collected extensive medical data on the participants. “Individuals were selected to have a disease endpoint of interest or an extreme trait value of public health importance,” said Dr. Leal.

By sequencing the exomes of 91 cystic fibrosis patients, Dr. Leal and her research colleagues discovered and replicated an association between variants in the DCTN4 gene and when a patient first develops a Pseudomonas aeruginosa airway infection.

The researchers were also able to replicate many known associations between individual DNA variants and traits, such as high blood levels of low-density lipoprotein, known as the ‘bad’ cholesterol, and C-reactive protein, which increases the body’s response to inflammation.

The majority of these findings are for variants that are common in the population, said Dr. Leal.

To detect associations with rare variants, analyses were performed by aggregating information from individual variants within a gene. This approach successfully detected an association with rare variants in the APOC3 gene that lowers triglyceride levels, an unhealthy type of fat in the blood, said Dr. Leal.

“In order to detect associations with rare variants, due to their modest effects, very large samples sizes are required. In many cases the data from the Exome Sequencing Project gave us leads that had to be evaluated using more study subjects. One mechanism for doing this was by genotyping additional samples using the exome chip, which contains approximately 240,000 coding variants. The Exome Sequencing Project played a very important role in the development of the exome chip, by being the largest contributor of data,” she added.

According to the NHLBI, exome sequencing is an efficient way to search for rare variants associated with complex traits. In contrast to previous genome wide association studies (GWAS), which concentrated on common variants scattered throughout the genome, exome sequencing has the potential to accelerate the search for unambiguous genetic links to disease by focusing attention on the protein coding portion of the genome

In the journal Science, Dr. Leal and her colleagues wrote that GWAS have substantially improved knowledge about common genetic variation, but have been generally uninformative about the patterns of rare variation within the protein coding regions of the genome.

“This is a very new field for which new methodology had to be developed. We learned many lessons in the quality control and analysis of exome data, as well as what types of results one would expect to see when analyzing rare variants. Additionally, the Exome Sequencing Project has been extremely valuable in obtaining a better understanding of population genomics and the history of man,” Dr. Leal said.

source : http://www.news-medical.net/news/20121107/Researchers-sequence-the-DNA-of-6700-exomes-of-cystic-fibrosis-patients.aspx

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Researchers succeed in teaching computers how to identify commonalities in DNA sequences

Researchers succeed in teaching computers how to identify commonalities in DNA sequences

Johns Hopkins researchers have succeeded in teaching computers how to identify commonalities in DNA sequences known to regulate gene activity, and to then use those commonalities to predict other regulatory regions throughout the genome. The tool is expected to help scientists better understand disease risk and cell development.

The work was reported in two recent papers in Genome Research, published online on July 3 and Sept. 27.

“Our goal is to understand how regulatory information is encrypted and to learn which sequence variations contribute to medical risks,” says Andrew McCallion, Ph.D., associate professor of molecular and comparative pathobiology in the McKusick-Nathans Institute of Genetic Medicine at Hopkins. “We give data to a computer and ‘teach it’ to distinguish between data that has no biological value versus data that has this or that biological value. It then establishes a set of rules, which allows it to look at new sets of data and apply what it learned. We’re basically sending our computers to school.”

These state-of-the-art “machine learning” techniques were developed by Michael Beer, Ph.D., assistant professor of biomedical engineering at the Johns Hopkins School of Medicine, and by Ivan Ovcharenko, Ph.D., at the National Center for Biotechnology Information. The researchers began both studies by creating “training sets” for their computers to “learn” from. These training sets were lists of DNA sequences taken from regions of the genome, called enhancers, that are known to increase the activity of particular genes in particular cells.

For the first of their studies, McCallion’s team created a training set of enhancer sequences specific to a particular region of the brain by compiling a list of 211 published sequences that had been shown, by various studies in mice and zebrafish, to be active in the development or function of that part of the brain.

For a second study, the team generated a training set through experiments of their own. They began with a purified population of mouse melanocytes, which are the skin cells that produce the pigment melanin that gives color to skin and absorbs harmful UV rays from the sun. The researchers used a technique called ChIP-seq (pronounced “chip seek”) to collect and sequence all of the pieces of DNA that were bound in those cells by special enhancer-binding proteins, generating a list of about 2,500 presumed melanocyte enhancer sequences.

Once the researchers had these two training sets for their computers, one specific to the brain and another to melanocytes, the computers were able to distinguish the features of the training sequences from the features of all other sequences in the genome, and create rules that defined one set from the other. Applying those rules to the whole genome, the computers were able to discover thousands of probable brain or melanocyte enhancer sequences that fit the features of the training sets.

In the brain study, the computers identified 40,000 probable brain enhancer sequences; for melanocytes, 7,500. Randomly testing a subset of each batch of sequences, the scientists found that more than 85 percent of the predicted enhancer sequences enhanced gene activity in the brain or in melanocytes, as expected, verifying the predictive power of their approach.

The researchers say that, in addition to identifying specific DNA sequences that control the genetic activity of a particular organ or cell type, these studies contribute to our understanding of enhancers in general and have validated an experimental approach that can be applied to many other biological questions as well.

Source : http://www.news-medical.net/news/20121107/Researchers-succeed-in-teaching-computers-how-to-identify-commonalities-in-DNA-sequences.aspx

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Positive results from BioCardia’s Helical Infusion System Phase 1/2 trial on ischemic cardiomyopathy

Positive results from BioCardia’s Helical Infusion System Phase 1/2 trial on ischemic cardiomyopathy

BioCardia, Inc., focused on regenerative biologic therapies for cardiovascular disease, today announced positive results from a Phase 1/2 heart failure trial using the Company’s Helical Infusion System, comprising the Helical Infusion System Catheter™ and Morph® Vascular Access Catheter, to deliver allogeneic, or “off-the-shelf,” and autologous, or from the treated patient, mesenchymal (adult) stem cells (MSCs) via transendocardial injection. According to the results, both the allogeneic and autologous MSCs were safe and well-tolerated at all doses and demonstrated similarly positive effects on cardiac structure and function, patient functional capacity and quality of life. Results from the POSEIDON (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis) study were reported in a late breaker presentation titled, “Randomized Comparison of Allogeneic vs Autologous Mesenchymal Stem Cells in Patients with Ischemic Cardiomyopathy,” at the American Heart Association’s 2012 Scientific Sessions and have been published in an article in the November 6 edition of the Journal of the American Medical Association. The POSEIDON study was cosponsored by the NIH Specialized Center for Cell Therapy, the University of Miami, and BioCardia.

Joshua Hare, M.D., Director of the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami Miller School of Medicine, and the POSEIDON study lead principal investigator, stated, “The combination of Allogenic MSCs with the BioCardia Helix catheter has enormous potential as a combination product for treating heart failure. The strong safety results and ease of the catheter delivery procedure in skilled hands, coupled with the potential for the use of allogeneic stem cells, suggest that this procedure may one day be as easy to perform as coronary angioplasty.”

Peter Altman, Ph.D., President and CEO of BioCardia, commented, “The Helical Infusion System is intended to be the safest and easiest to use catheter for multiple clinical applications in cell- and gene-based therapy. We believe its performance and our track record of experience are second to none, and we are very optimistic about the delivery mesenchymal stem cells for the treatment of ischemic heart failure. Trial results such as POSEIDON require the talent and hard work of a dedicated team of experts, and we have been privileged to work with the clinical teams at the University of Miami and Johns Hopkins University.”

Interventional cardiologist co-authors who performed the procedures in the study included Alan W. Heldman, M.D., and Juan Pablo Zambrano, M.D., at the University of Miami Miller School of Medicine, and Jeffrey A Brinker, M.D., and Peter VanDoren Johnston, M.D., at the Johns Hopkins University School of Medicine.

The Phase 1/2 POSEIDON study enrolled 31 patients with chronic ischemic left ventricular (LV) dysfunction due to ischemic cardiomyopathy (ICM). Patients were randomized to receive one of three different dose levels (20, 100, or 200 million cells) of either allogeneic MSCs or autologous MSCs. The stem cells were delivered to 10 LV sites in the myocardium by BioCardia’s transendocardial stem cell injection (TESI) during retrograde left heart catheterization using BioCardia’s Helical Infusion Catheter. The two catheter system fixates to the heart wall via a corkscrew needle, allowing for stable and controlled delivery of biologic therapies to the heart.

Following BioCardia’s TESI, patients were hospitalized for a minimum of four days and were seen two weeks post-catheterization. Thereafter, safety and efficacy assessments using cardiac imaging studies, exercise peak VO2, a 6-minute walk test, New York Heart Association (NYHA) Class and the Minnesota Living with Heart Failure (MLHF) questionnaire were performed on a monthly basis for six months and then again at 12 months. After 13 months, all patients received follow-up CT scans of the heart, chest, abdomen and pelvis.

The primary objective of the study was to demonstrate the safety of allogeneic MSCs administered by BioCardia’s TESI, determined by the incidence of any treatment-emergent serious adverse events (TE-SAEs) one month after stem cell injection. Data showed that within 30 days, one patient in each cohort was hospitalized for heart failure, a TE-SAE rate of 6.7%, substantially less than the pre-specified stopping rate of 25%. The secondary objectives were to compare the long-term safety of allogeneic MSCs to autologous MSCs and to demonstrate the efficacy of allogeneic MSCs and autologous MSCs administered by TESI in these patients. The one-year incidence of serious adverse events was not different between cell types, except for fewer ventricular arrhythmias in allogeneic recipients. Relative to baseline, allogeneic and autologous MSC therapy similarly improved the 6-minute walk and the MLHF questionnaire score, but not the exercise VO2 max. Finally, MSCs reduced infarct size (33.2%; P<0.0001), left ventricular (LV) volumes and sphericity index similarly in allogeneic and autologous groups. Importantly, allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions.

A parallel Phase 1/2 study – the Transendocardial Autologous Cells in Heart Failure Trial (TAC-HFT) – also enabled by the BioCardia Helical Infusion System. The trial, co-sponsored by the University of Miami, is comparing autologous (bone marrow or mesenchymal) cell delivery to placebo in up to 68 cardiomyopathy patients randomized under a protocol similar to that of the POSEIDON trial. Early results in a first cohort of patients (N=8) were reported in 2011 to show that the autologous cells effected remodeling of LV shape and restoration of normal LV proportions.

Source : http://www.news-medical.net/news/20121107/Positive-results-from-BioCardias-Helical-Infusion-System-Phase-12-trial-on-ischemic-cardiomyopathy.aspx

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New tool can particularly sort tumor-causing cancer cells

New tool can particularly sort tumor-causing cancer cells

A new tool developed by scientists at The Methodist Hospital separates tumor-causing cancer cells from more benign cells by subjecting the cells to a microscopic game of Plinko — except only the squishiest cells make it through.

As reported in this week’s Proceedings of the National Academy of Sciences (early edition online), the more flexible, tumor-causing cells navigated a gamut of tiny barriers, whereas the more rigid, more benign cells had trouble squeezing through 7 micrometer holes. Methodist scientists worked with University of Texas MD Anderson Cancer Center researchers to test the device with different kinds of cancer cells.

The work supports the hypothesis that cell squishiness indicates tumor potential. Most normal cells contain a developed cytoskeleton — a network of tiny but strong rod-shaped proteins that give cells their shape and structure. In their feverish drive to divide, cancer cells may be diverting resources away from developing a cytoskeleton in favor of division, hence the squishiness.

“We have created many pathways for cells to cross barriers,” said Methodist nanomedical faculty Lidong Qin, Ph.D., the project’s principal investigator. “The throughput of a MS-Chip is at the level of one million cells. When a stiff cell blocks one particular barrier, many other bypasses will allow flexible cells to flow through.”

Cancer stem cells are known to be squishier than other cancer cells. The team of scientists showed that flexible cells separated by the MS-Chip exhibited gene expression patterns consistent with cancer stem cells.

“Many papers indicate the presence of cancer stem cells means a worse prognosis for patients,” said cancer scientist Jenny Chang, M.D., co-principal investigator and director of Methodist’s Cancer Center. “Yet they are not typically quantified by doctors.”

Subsequent analysis of separated cells by the Methodist and MD Anderson team showed the flexible cells were less likely to express cell cytoskeleton genes and more likely to express the motility genes that could contribute to metastasis.

By testing for the presence of metastatic cells, doctors may be able to tell whether cancer treatment was successful, or an as-yet untreated cancer’s likelihood of metastasizing to another part of the body.

A growing awareness of cancer stem cells’ role in cancer metastasis and recurrence and has been frustrated by the absence of technology that makes this knowledge useful to doctors and their patients. Up to now, there has been no way of quickly and reliably separating and identifying the more dangerous tumor-causing cells from a biopsy.

The new device, which was developed at Methodist, successfully enriched tumor-causing cells from a mixture of cancer cells. It is called the Mechanical Separation Chip, or MS-Chip. Cells separated by the device can be easily collected and studied. The current standard for cell separation, flow cytometry, is relatively slow and relies on cell surface biomarkers.

“Our microfluidics cell separation via MS-Chip provides a high throughput method that can particularly sort cells to different levels of stiffness, which opens a new avenue to study stiffness related cellular and molecular biology,” Qin said. “Downstream molecular analysis, including genomic and proteomic profiling of the cell subtypes, provides an approach to identifying new biomarkers relevant to cancer stem cells and cancer metastasis.”

Right now, each MS-Chip costs about $10 to produce.

“If massively produced, MS-Chip cost could be at the level of one dollar per chip,” Qin said. “Running a mechanical cell separation will be even less expensive than flow cytometry cell sorting.”

Source : http://www.news-medical.net/news/20121103/New-tool-can-particularly-sort-tumor-causing-cancer-cells.aspx

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Mass spectrometry can help visualize how drugs work inside living cells to kill infectious microbes

Mass spectrometry can help visualize how drugs work inside living cells to kill infectious microbes

Weill Cornell Medical College researchers report that mass spectrometry, a tool currently used to detect and measure proteins and lipids, can also now allow biologists to “see” for the first time exactly how drugs work inside living cells to kill infectious microbes. As a result, scientists may be able to improve existing antibiotics and design new, smarter ones to fight deadly infections, such as tuberculosis. The new study was published in today’s early online edition of Science.

“The development of antibiotics has been stalled for several decades and many infectious microbes have become drug-resistant,” says the study’s senior investigator, Dr. Kyu Y. Rhee, an infectious disease expert who is an associate professor of medicine in the Division of Infectious Diseases and associate professor of microbiology and immunology at Weill Cornell Medical College. “We must restock the antibiotic pipeline and our study findings provide a powerful new approach for doing just that.”

The need to develop new antibiotics is perhaps nowhere more pressing than for the treatment of tuberculosis, TB, which is the single leading bacterial cause of death worldwide, and with the emergence of now total drug resistance, an unchecked global public health emergency.

“Current TB treatments are long and complex, lasting a minimum of six months, and often resulting in treatment failures and the paradoxical emergence of multi-drug resistance,” says Dr. Rhee, who is also an associate attending physician at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. “We are still using the antibiotics that were first developed for TB about 50 years ago.”

Most TB drugs — as well as antibiotics for other infections — were developed through a combination of empirical approaches, Dr. Rhee explains. “However, it had been impossible to know what the drug was doing inside the bacteria.”

That situation has now changed. Dr. Rhee and his colleagues, who include investigators from the National Institutes of Health, applied modern technologies that stem from use of mass spectrometry to directly visualize what happens when these drugs infiltrate TB cells. They can “watch,” at a basic biochemical level, what happens to both the antibiotic agent and infecting bacteria over time after the drug is administered.

Mass spectrometry, simply stated, is a tool that weighs individual molecules as a way to identify them. It was first used in physics, but has expanded to many disciplines to help scientists identify molecules and determine the quantity of each kind in gases, liquids, as well as solids. Advances in mass spectrometry have made it possible for biologists to leverage the tool in the last few years, and, with this study, evaluate the intracellular fates and actions of small drug molecules.

This study is the first to show mass spectrometry can also be adapted to understand the action of antibiotics on living, intact bacterial cells.

In the study, Dr. Rhee’s research team exposed TB to para-aminosalicylic acid (PAS), which was developed more than 50 years ago, and is still part of the multi-drug regimen used to treat resistant TB. It is the second oldest TB drug on the market.

The drug was thought to work by inhibiting an enzyme used by bacteria to synthesize folates, an essential class of nutrients that humans acquire by eating, but bacteria must make on their own. “Many thus believed that the drug interfered with folate synthesis in the TB bacterium by functioning as an occlusive plug that blocked this pathway,” says Dr. Rhee.

However, researchers actually found, while it is true PAS prevents the utilization of the natural precursors used to synthesize folates, once inside TB, PAS itself also turns toxic. “PAS is an agent that uses the TB cell’s machinery to turn it into a poison. Thus, it doesn’t simply kill the cell by stopping its food supply, it also morphs into a lethal drug,” Dr. Rhee says.

The researchers also tested a different drug, sulfonamide (sulfa), which is an 80-year-old class of antibacterial agents known to defeat many infections, but not TB successfully.

“Scientists thought sulfa didn’t penetrate TB cells, but we witnessed, using mass spectrometry, that it did, in fact, enter the bacteria. But that once inside, TB bacteria were able to degrade the drug,” Dr. Rhee says. This finding suggests to researchers that it might be possible to modify the sulfa molecule so that it can withstand degradation by TB bacteria.

“Both of these findings were completely unexpected,” says Dr. Rhee. “The study findings show us that sometimes there is a profound disconnect between what we think a drug is doing and how it actually works inside cells.”

“The power of mass spectrometry is now evident, and we can’t wait to use it to test all of the current cocktail of drugs used to treat TB to find ways to improve them,” Dr. Rhee says. “Best of all will be the use of this tool to design and test the much-needed next generation of effective anti-TB agents.”

Source : http://www.news-medical.net/news/20121103/Mass-spectrometry-can-help-visualize-how-drugs-work-inside-living-cells-to-kill-infectious-microbes.aspx

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Fluidigm unveils four innovative devices to meet challenges associated with production genomics

Fluidigm unveils four innovative devices to meet challenges associated with production genomics

Fluidigm Corporation (NASDAQ:FLDM) today introduced four new integrated fluidic circuits (IFCs) designed to meet the challenges associated with production genomics. These new offerings are expected to make substantial contributions to laboratories performing high sample throughput digital PCR, genotyping, and targeted panel testing.

“Today, we unveil four innovative devices, each responding to unmet needs in production genomics. To deliver ultra-low cost per sample and exquisite accuracy in digital PCR, we introduce the qdPCR™ 37K IFC. To minimize sample re-work and ambiguous results in high-throughput genotyping, we now offer the High-Precision 96.96 Genotyping IFC. To enable high sample throughput for gene expression applications, we announce the 192.24 Gene Expression IFC. Finally, in response to many requests for greater sample and assay flexibility during target selection, we present the FLEXsix™ Gene Expression IFC, first of a family of flexible, configurable IFCs,” said Gajus Worthington, Fluidigm President and Chief Executive Officer.

With these new IFCs, the BioMark™ HD system now supports the entire span of activity from target selection through production scale-up, eliminating the need for technology-bridging studies.

The Fluidigm qdPCR 37K IFC

The qdPCR 37K IFC combines both digital and quantitative real-time PCR. Real-time analysis of digital PCR reactions minimizes false positives. The qdPCR 37K IFC also provides high amplification success rate with the lowest cost-per-sample available in the market today, as low as $2 per sample.

Droplet and spotted-array based digital methods often experience high “drop-out” rates that can adversely impact their ability to detect target sequences. The qdPCR 37K IFC performs at a 99.9% success rate, providing ultra-high precision and throughput without the concern of false positives. This is especially critical in high-sensitivity applications, such as rare mutation detection, GMO testing, and aneuploidy detection.

With the qdPCR 37K IFC, researchers can enjoy a nearly 80% savings per sample when their applications require four-plex tests per sample. Other products on the market only provide a two-plex solution, meaning each sample would have to be run multiple times, adding cost and decreasing throughput.

The High-Precision 96.96 Genotyping IFC

The High-Precision 96.96 Genotyping IFC is the highest quality genotyping product available today exhibiting a minimum call rate of 99.9%. This precision is vital to production and human genomics laboratories where every SNP for every sample matters.

Some other platforms claim a 95% call rate. If a production genotyping lab is running 96 SNPs per sample, this implies, statistically, that there is only a one-percent chance that all of their 96 SNPs will be “called” on a particular sample. This can lead to extensive re-work, uncertain results, and low overall sample yield. In contrast, when using Fluidigm’s new High-Precision 96.96 Genotyping IFC, the likelihood that all 96 SNPs are “called” climbs to 91%.

The High-Precision 96.96 Genotyping IFC and BioMark HD system deliver standard-setting performance while also enabling high-sample throughput with an easy workflow—one operator can easily deliver more than 36,000 data points in a day.

192.24 Gene Expression IFC

The Fluidigm 192.24 Gene Expression IFC meets the needs of production users who have narrowed their gene panel and require high sample throughput. Together with the BioMark HD system, this IFC enables throughput of 576 samples across 24 genes in an 8-hour day, with minimal hands-on time. The 192.24 Gene Expression IFC can be particularly useful in clinical research and production environment, where users will benefit from the low-cost per sample, high reliability and simple workflow of the new 192.24 Gene Expression IFC.

The Fluidigm FLEXsix Gene Expression IFC addresses the requirement for substantial variation in sample and assay numbers during target selection while allowing complete use of the IFC. It utilizes a completely new architecture which incorporates six 12 X 12 partitions that can be organized in any configuration, in up to six separate experimental runs. For example, a single IFC could initially run a 12-sample by 48-gene experiment, followed by a 24-sample by 12-gene experiment, followed by two separate 12-sample by 12-gene experiments. This new IFC adjusts to customers’ experimental needs during target selection and largely eliminates the need for microplate-based experiments.

The initial version of the FLEXsix IFC supports gene expression studies, but the architecture will ultimately support genotyping as well.

Production laboratories have a critical need to scale from target selection to production as quickly and cost-effectively as possible. Other platforms require technology-bridging studies as the lab’s volume scales up. This adds time, cost and substantial risk. Fluidigm provides a complete range of IFC products that eliminates the challenges faced in production genomics by supplying a single technology platform—integrated fluidic circuits—that scales from target selection to production.

Availability

The qdPCR 37K IFC and the High-Precision 96.96 Genotyping IFC are available now. Fluidigm will be profiling these products in detail at the American Society of Human Genetics (ASHG) Annual Meeting in San Francisco starting November 6, 2012. Fluidigm will host an ASHG workshop from 12:45 p.m. – 2:15 p.m., in the Moscone Center, Room 307, Esplanade Level South on Friday, November 9, 2012.

The Fluidigm 192.24 Gene Expression IFC is expected to be available in December 2012. The Fluidigm FLEXsix IFC is expected to be available in January 2013.

Source : http://www.news-medical.net/news/20121102/Fluidigm-unveils-four-innovative-devices-to-meet-challenges-associated-with-production-genomics.aspx

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