2,378 results on '"Bioinformatics"'
Search Results
2. Four change-makers seek impact in medical research.
- Author
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Coombs, Amy and Ong, Sandy
- Abstract
Bringing fresh perspectives to long-standing health challenges, these scientists are using techniques such as big-data analytics and AI to push the field. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. How open-source software could finally get the world’s microscopes speaking the same language.
- Author
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Brooks, Michael
- Abstract
A plethora of standards mean shareable and verifiable microscopy data often get lost in translation. Biologists are working on a solution. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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- View/download PDF
4. How to share data — not just equally, but equitably.
- Abstract
Just as with many natural resources, wealthy countries have been extracting scientific data from poorer nations for centuries. Researchers are changing that. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
5. Want to track pandemic variants faster? Fix the bioinformatics bottleneck.
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Hodcroft, Emma B., De Maio, Nicola, Lanfear, Rob, MacCannell, Duncan R., Minh, Bui Quang, Schmidt, Heiko A., Stamatakis, Alexandros, Goldman, Nick, and Dessimoz, Christophe
- Abstract
Tools, rules and incentives are buckling under the flood of coronavirus genome sequences — to help control the pandemic, researchers need new approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
6. 'Wildly weird' RNA bits discovered infesting the microbes in our guts.
- Author
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Sidik S
- Published
- 2024
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- View/download PDF
7. Methods section too short? Use online protocols to make complex techniques understandable.
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Borm L
- Published
- 2023
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8. Embracing the command line: my unexpected career in computational biology.
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Tang MT
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- 2023
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- View/download PDF
9. How to spice up your bioinformatics skill set with AI.
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Pells R
- Subjects
- Computational Biology education, Computational Biology methods, Data Analysis, Machine Learning, Research Personnel education
- Published
- 2023
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- View/download PDF
10. Men dominate conference Q&A sessions — including online ones.
- Author
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Gulland, Anne
- Abstract
‘Question and manswer’ sessions are the norm at both in-person and virtual events, even when there’s a good gender balance. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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11. A clinically applicable integrative molecular classification of meningiomas
- Author
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Vikas Patil, Rupert Hugh-White, Thomas Kislinger, Bharati Mehani, Kenneth Aldape, Daniel D. De Carvalho, Caroline Y. Chen, Andrew Macklin, Ankur Chakravarthy, Qingxia Wei, Gary D. Bader, Lydia Y Liu, Rosario I. Corona, Paul C. Boutros, Adriana M. Workewych, Justin Z. Wang, Suganth Suppiah, Jeffrey C Liu, Yasin Mamatjan, Ghazaleh Tabatabai, Shirin Karimi, Farshad Nassiri, Andrew Gao, Gelareh Zadeh, Olivia Singh, and Shahbaz Khan
- Subjects
Mutation ,Multidisciplinary ,business.industry ,Point mutation ,Disease ,medicine.disease ,Proteogenomics ,Bioinformatics ,medicine.disease_cause ,Meningioma ,DNA methylation ,medicine ,Immunohistochemistry ,Cancer epigenetics ,business - Abstract
Meningiomas are the most common primary intracranial tumour in adults1. Patients with symptoms are generally treated with surgery as there are no effective medical therapies. The World Health Organization histopathological grade of the tumour and the extent of resection at surgery (Simpson grade) are associated with the recurrence of disease; however, they do not accurately reflect the clinical behaviour of all meningiomas2. Molecular classifications of meningioma that reliably reflect tumour behaviour and inform on therapies are required. Here we introduce four consensus molecular groups of meningioma by combining DNA somatic copy-number aberrations, DNA somatic point mutations, DNA methylation and messenger RNA abundance in a unified analysis. These molecular groups more accurately predicted clinical outcomes compared with existing classification schemes. Each molecular group showed distinctive and prototypical biology (immunogenic, benign NF2 wild-type, hypermetabolic and proliferative) that informed therapeutic options. Proteogenomic characterization reinforced the robustness of the newly defined molecular groups and uncovered highly abundant and group-specific protein targets that we validated using immunohistochemistry. Single-cell RNA sequencing revealed inter-individual variations in meningioma as well as variations in intrinsic expression programs in neoplastic cells that mirrored the biology of the molecular groups identified. Multi-omics datasets are integrated to generate a unified and clinically informed molecular classification of meningiomas.
- Published
- 2021
12. The changing landscape of atherosclerosis
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Peter Libby
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Emerging risk ,Disease ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Bioinformatics ,Models, Biological ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,medicine ,Animals ,Humans ,030212 general & internal medicine ,Microbiome ,Risk factor ,Inflammation ,Multidisciplinary ,business.industry ,Cholesterol ,Altered behaviour ,Atherosclerosis ,Vulnerable plaque ,Plaque, Atherosclerotic ,chemistry ,Disease Susceptibility ,business ,Lipoprotein - Abstract
Emerging evidence has spurred a considerable evolution of concepts relating to atherosclerosis, and has called into question many previous notions. Here I review this evidence, and discuss its implications for understanding of atherosclerosis. The risk of developing atherosclerosis is no longer concentrated in Western countries, and it is instead involved in the majority of deaths worldwide. Atherosclerosis now affects younger people, and more women and individuals from a diverse range of ethnic backgrounds, than was formerly the case. The risk factor profile has shifted as levels of low-density lipoprotein (LDL) cholesterol, blood pressure and smoking have decreased. Recent research has challenged the protective effects of high-density lipoprotein, and now focuses on triglyceride-rich lipoproteins in addition to low-density lipoprotein as causal in atherosclerosis. Non-traditional drivers of atherosclerosis—such as disturbed sleep, physical inactivity, the microbiome, air pollution and environmental stress—have also gained attention. Inflammatory pathways and leukocytes link traditional and emerging risk factors alike to the altered behaviour of arterial wall cells. Probing the pathogenesis of atherosclerosis has highlighted the role of the bone marrow: somatic mutations in stem cells can cause clonal haematopoiesis, which represents a previously unrecognized but common and potent age-related contributor to the risk of developing cardiovascular disease. Characterizations of the mechanisms that underpin thrombotic complications of atherosclerosis have evolved beyond the ‘vulnerable plaque’ concept. These advances in our understanding of the biology of atherosclerosis have opened avenues to therapeutic interventions that promise to improve the prevention and treatment of now-ubiquitous atherosclerotic diseases. This Review discusses recent research that has transformed our understanding of the biology of atherosclerosis, and examines its implications for the treatment of atherosclerotic cardiovascular disease.
- Published
- 2021
13. Gene therapies close in on a cure for sickle-cell disease
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Michael Eisenstein
- Subjects
2019-20 coronavirus outbreak ,Multidisciplinary ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Genetic enhancement ,Cell ,Genomics ,Disease ,Bioinformatics ,medicine.anatomical_structure ,medicine ,business ,Gene - Abstract
As multiple genetic strategies advance through the clinic, important safety questions remain to be answered. As multiple genetic strategies advance through the clinic, important safety questions remain to be answered.
- Published
- 2021
14. Deranged chromatin drives uterine fibroid tumours
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Zehra Ordulu
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Multidisciplinary ,Uterine fibroids ,business.industry ,medicine ,Epigenetics ,medicine.disease ,business ,Bioinformatics ,Chromatin - Abstract
A previously unknown subgroup of uterine fibroid tumours is driven by mutations that result in disruption of the DNA–protein complex chromatin. The findings could inform the management of this common condition. Molecular categories of common benign uterine tumours defined.
- Published
- 2021
15. Why call it BA.2.12.1? A guide to the tangled Omicron family.
- Author
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Maxmen, Amy
- Abstract
Nature explores how subvariants are named, and why none of Omicron’s family members has been upgraded to a ‘variant of concern’. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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16. Host variables confound gut microbiota studies of human disease
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Loki Natarajan, Jack Sklar, Rob Knight, Lingjing Jiang, Ivan Vujkovic-Cvijin, and Yasmine Belkaid
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0301 basic medicine ,Male ,Data Analysis ,Disease ,Gut flora ,Bioinformatics ,Oral and gastrointestinal ,Body Mass Index ,Machine Learning ,Feces ,0302 clinical medicine ,Residence Characteristics ,RNA, Ribosomal, 16S ,80 and over ,2.1 Biological and endogenous factors ,Young adult ,Aetiology ,Aged, 80 and over ,Multidisciplinary ,biology ,Confounding ,Human microbiome ,Confounding Factors, Epidemiologic ,Middle Aged ,Area Under Curve ,Female ,Type 2 ,Adult ,16S ,Alcohol Drinking ,General Science & Technology ,Concordance ,digestive system ,Article ,03 medical and health sciences ,Young Adult ,Diabetes Mellitus ,Genetics ,Humans ,Microbiome ,Life Style ,Aged ,Ribosomal ,Epidemiologic ,Human Genome ,Case-control study ,biology.organism_classification ,Confounding Factors ,Diet ,Gastrointestinal Microbiome ,030104 developmental biology ,Good Health and Well Being ,Diabetes Mellitus, Type 2 ,ROC Curve ,Case-Control Studies ,RNA ,Gastrointestinal Motility ,030217 neurology & neurosurgery - Abstract
Low concordance between studies that examine the role of microbiota in human diseases is a pervasive challenge that limits the capacity to identify causal relationships between host-associated microorganisms and pathology. The risk of obtaining false positives is exacerbated by wide interindividual heterogeneity in microbiota composition1, probably due to population-wide differences in human lifestyle and physiological variables2 that exert differential effects on the microbiota. Here we infer the greatest, generalized sources of heterogeneity in human gut microbiota profiles and also identify human lifestyle and physiological characteristics that, if not evenly matched between cases and controls, confound microbiota analyses to produce spurious microbial associations with human diseases. We identify alcohol consumption frequency and bowel movement quality as unexpectedly strong sources of gut microbiota variance that differ in distribution between healthy participants and participants with a disease and that can confound study designs. We demonstrate that for numerous prevalent, high-burden human diseases, matching cases and controls for confounding variables reduces observed differences in the microbiota and the incidence of spurious associations. On this basis, we present a list of host variables that we recommend should be captured in human microbiota studies for the purpose of matching comparison groups, which we anticipate will increase robustness and reproducibility in resolving the members of the gut microbiota that are truly associated with human disease.
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- 2020
17. Huge cache of mammal genomes offers fresh insights on human evolution.
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Kozlov M
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- 2023
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18. 'Touch-taste': how the octopus repurposed its nervous system to hunt.
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Fox D
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- 2023
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19. A molecular connection hints at how a genetic risk factor drives Crohn’s disease
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Scott Plevy
- Subjects
0301 basic medicine ,Crohn's disease ,Multidisciplinary ,Disease ,Biology ,Bioinformatics ,medicine.disease ,Medical research ,digestive system diseases ,Connection (mathematics) ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,NOD2 ,medicine ,030211 gastroenterology & hepatology ,Genetic risk factor ,Nod2 gene - Abstract
Mutations of the NOD2 gene are risk factors for Crohn’s disease. Many aspects of how they contribute to the condition are unknown. The discovery of cell populations that are involved suggests new therapeutic options. Cell populations shed light on how NOD2 mutations contribute to disease.
- Published
- 2021
20. Host–microbiota maladaptation in colorectal cancer
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Elizabeth H. Mann, Alina Janney, and Fiona Powrie
- Subjects
Inflammation ,0301 basic medicine ,Multidisciplinary ,Colorectal cancer ,Disease ,Biology ,medicine.disease ,Bioinformatics ,Intestinal epithelium ,Gastrointestinal Microbiome ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Mutagenesis ,030220 oncology & carcinogenesis ,Bystander effect ,Disease risk ,medicine ,Animals ,Dysbiosis ,Humans ,Colorectal Neoplasms ,Maladaptation - Abstract
Colorectal cancer (CRC) is a heterogeneous disease of the intestinal epithelium that is characterized by the accumulation of mutations and a dysregulated immune response. Up to 90% of disease risk is thought to be due to environmental factors such as diet, which is consistent with a growing body of literature that describes an 'oncogenic' CRC-associated microbiota. Whether this dysbiosis contributes to disease or merely represents a bystander effect remains unclear. To prove causation, it will be necessary to decipher which specific taxa or metabolites drive CRC biology and to fully characterize the underlying mechanisms. Here we discuss the host-microbiota interactions in CRC that have been reported so far, with particular focus on mechanisms that are linked to intestinal barrier disruption, genotoxicity and deleterious inflammation. We further comment on unknowns and on the outstanding challenges in the field, and how cutting-edge technological advances might help to overcome these. More detailed mechanistic insights into the complex CRC-associated microbiota would potentially reveal avenues that can be exploited for clinical benefit.
- Published
- 2020
21. A substrate-specific mTORC1 pathway underlies Birt–Hogg–Dubé syndrome
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Jlenia Monfregola, Pier Paolo Di Fiore, Maria Matarese, Marcella Cesana, Lukas A. Huber, Angela Zampelli, Salvatore Pece, Giovanni Bertalot, Mariana E. G. de Araujo, Taras Stasyk, Edoardo Nusco, Chiara Di Malta, Diletta Siciliano, Alessandro Venuta, Gennaro Napolitano, Claudia Vilardo, Valerio Benedetti, Alessia Calcagni, Alessandra Esposito, Andrea Ballabio, Napolitano, G., Di Malta, C., Esposito, A., de Araujo, M. E. G., Pece, S., Bertalot, G., Matarese, M., Benedetti, V., Zampelli, A., Stasyk, T., Siciliano, D., Venuta, A., Cesana, M., Vilardo, C., Nusco, E., Monfregola, J., Calcagni, A., Di Fiore, P. P., Huber, L. A., and Ballabio, A.
- Subjects
0301 basic medicine ,Urology ,MEDLINE ,P70-S6 Kinase 1 ,mTORC1 ,Mechanistic Target of Rapamycin Complex 1 ,Bioinformatics ,Birt–Hogg–Dubé syndrome ,Article ,Cell Line ,Substrate Specificity ,Birt-Hogg-Dube Syndrome ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Proto-Oncogene Proteins ,Tuberous Sclerosis Complex 2 Protein ,medicine ,Animals ,Humans ,Phosphorylation ,Folliculin ,Kinase activity ,Mechanistic target of rapamycin ,Monomeric GTP-Binding Proteins ,Mice, Knockout ,Multidisciplinary ,biology ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,business.industry ,Tumor Suppressor Proteins ,medicine.disease ,Kidney Neoplasms ,Cell biology ,Enzyme Activation ,Disease Models, Animal ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,TFEB ,Ras Homolog Enriched in Brain Protein ,biological phenomena, cell phenomena, and immunity ,business ,Differential (mathematics) ,Signal Transduction ,HeLa Cells ,Protein Binding ,RHEB - Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) is a key metabolic hub that controls the cellular response to environmental cues by exerting its kinase activity on multiple substrates1–3. However, whether mTORC1 responds to diverse stimuli by differentially phosphorylating specific substrates is poorly understood. Here we show that transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy4,5, is phosphorylated by mTORC1 via a substrate-specific mechanism that is mediated by Rag GTPases. Owing to this mechanism, the phosphorylation of TFEB—unlike other substrates of mTORC1, such as S6K and 4E-BP1— is strictly dependent on the amino-acid-mediated activation of RagC and RagD GTPases, but is insensitive to RHEB activity induced by growth factors. This mechanism has a crucial role in Birt–Hogg–Dube syndrome, a disorder that is caused by mutations in the RagC and RagD activator folliculin (FLCN) and is characterized by benign skin tumours, lung and kidney cysts and renal cell carcinoma6,7. We found that constitutive activation of TFEB is the main driver of the kidney abnormalities and mTORC1 hyperactivity in a mouse model of Birt–Hogg–Dube syndrome. Accordingly, depletion of TFEB in kidneys of these mice fully rescued the disease phenotype and associated lethality, and normalized mTORC1 activity. Our findings identify a mechanism that enables differential phosphorylation of mTORC1 substrates, the dysregulation of which leads to kidney cysts and cancer. Dysregulation of an mTORC1 substrate-specific mechanism leads to constitutive activation of TFEB, and promotes kidney cystogenesis and tumorigenesis in a mouse model of Birt–Hogg–Dube syndrome.
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- 2020
22. Dietary modifications for enhanced cancer therapy
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David M. Sabatini, Naama Kanarek, and Boryana Petrova
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0301 basic medicine ,Multidisciplinary ,business.industry ,Cancer therapy ,Cancer ,Cancer Microenvironment ,Nutritional status ,medicine.disease ,Bioinformatics ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Fructose metabolism ,Nutrient ,030220 oncology & carcinogenesis ,Cancer metabolism ,Medicine ,business ,Dietary modifications - Abstract
Tumours depend on nutrients supplied by the host for their growth and survival. Modifications to the host’s diet can change nutrient availability in the tumour microenvironment, which might represent a promising strategy for inhibiting tumour growth. Dietary modifications can limit tumour-specific nutritional requirements, alter certain nutrients that target the metabolic vulnerabilities of the tumour, or enhance the cytotoxicity of anti-cancer drugs. Recent reports have suggested that modification of several nutrients in the diet can alter the efficacy of cancer therapies, and some of the newest developments in this quickly expanding field are reviewed here. The results discussed indicate that the dietary habits and nutritional state of a patient must be taken into account during cancer research and therapy.
- Published
- 2020
23. Base editor repairs mutation found in the premature-ageing syndrome progeria
- Author
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Wilbert P. Vermeij, Jan H.J. Hoeijmakers, and Molecular Genetics
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congenital, hereditary, and neonatal diseases and abnormalities ,0303 health sciences ,Progeria ,Multidisciplinary ,integumentary system ,business.industry ,nutritional and metabolic diseases ,medicine.disease ,Bioinformatics ,03 medical and health sciences ,Premature ageing syndrome ,0302 clinical medicine ,embryonic structures ,Mutation (genetic algorithm) ,medicine ,business ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
No cure exists for the lethal premature-ageing condition Hutchinson–Gilford progeria. A gene-editing tool — adenine base editors — offers a way to treat the condition in mice. Could this approach lead to an effective therapy? Gene-editing method treats mouse model of Hutchinson–Gilford progeria.
- Published
- 2021
24. Landmark CRISPR trial shows promise against deadly disease
- Author
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Heidi Ledford
- Subjects
Multidisciplinary ,business.industry ,Genetic enhancement ,Medicine ,CRISPR ,Disease ,Bioinformatics ,business - Abstract
Administering gene-editing treatment directly into the body could be a safe and effective way to treat a rare, life-threatening condition. Administering gene-editing treatment directly into the body could be a safe and effective way to treat a rare, life-threatening condition.
- Published
- 2021
25. Base editor treats progeria in mice
- Author
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Francis S. Collins, Michael R. Erdos, David R. Liu, Jonathan D. Brown, Leslie B. Gordon, and Luke W. Koblan
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Progeria ,Multidisciplinary ,integumentary system ,business.industry ,Cardiovascular health ,nutritional and metabolic diseases ,Disease ,medicine.disease ,Bioinformatics ,LMNA ,embryonic structures ,Mutation (genetic algorithm) ,medicine ,business ,Base (exponentiation) - Abstract
A single dose of an adenine base editor shows promise in treating the ageing-related disease Hutchinson–Gilford progeria syndrome. It corrected the LMNA mutation underlying the disease in patient-derived cells and improved cardiovascular health and lifespan in mice. Single dose of adenine base editor shows promise in treating ageing-related syndrome.
- Published
- 2021
26. A cartoon guide to bioinformatics by a novice coder
- Author
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Ed Himelblau
- Subjects
ComputingMilieux_GENERAL ,Engineering ,Multidisciplinary ,business.industry ,Cartoonist ,media_common.cataloged_instance ,Geneticist ,business ,Bioinformatics ,Code (semiotics) ,media_common - Abstract
Ed Himelblau was a cartoonist before he learnt to write code. Now, the geneticist hopes his drawings will help others who embrace bioinformatics later in their careers. Ed Himelblau was a cartoonist before he learnt to write code. Now, the geneticist hopes his drawings will help others who embrace bioinformatics later in their careers.
- Published
- 2021
27. The future of tissue-agnostic drugs
- Author
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Julianna Photopoulos
- Subjects
03 medical and health sciences ,0302 clinical medicine ,Multidisciplinary ,business.industry ,030220 oncology & carcinogenesis ,medicine ,Cancer ,Genomics ,030212 general & internal medicine ,Personalized medicine ,Bioinformatics ,business ,medicine.disease - Abstract
Some people with cancer are already benefiting from drugs that target genetic features regardless of the tissue involved. But these early successes could be the exceptions. Some people with cancer are already benefiting from drugs that target genetic features regardless of the tissue involved. But these early successes could be the exceptions.
- Published
- 2020
28. Cystic fibrosis drugs target the malformed proteins at the root of the disease
- Author
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Sarah DeWeerdt
- Subjects
Multidisciplinary ,endocrine system diseases ,genetic structures ,business.industry ,Medicine ,Disease ,business ,Left behind ,medicine.disease ,Bioinformatics ,Cystic fibrosis ,eye diseases - Abstract
New combinations of molecules put many patients on the path to good health. But those with rarer mutations are, for now, left behind. New combinations of molecules put many patients on the path to good health. But those with rarer mutations are, for now, left behind.
- Published
- 2020
29. Dietary methionine influences therapy in mouse cancer models and alters human metabolism
- Author
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Ana Calcagnotto, Sydney M. Sanderson, John P. Richie, Peter G. Mikhael, Michael A. Reid, David S. Hsu, Samantha J. Mentch, Min Lu, Amy Ciccarella, David G. Kirsch, Gene P. Ables, Xia Gao, Juan Liu, Daniel E. Cooper, Sailendra N. Nichenametla, Jason W. Locasale, and Ziwei Dai
- Subjects
0301 basic medicine ,Multidisciplinary ,Methionine ,business.industry ,medicine.drug_class ,Colorectal cancer ,Cancer ,medicine.disease ,medicine.disease_cause ,Bioinformatics ,Antimetabolite ,3. Good health ,03 medical and health sciences ,Metabolic pathway ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,030220 oncology & carcinogenesis ,medicine ,KRAS ,Sarcoma ,business ,Flux (metabolism) - Abstract
Nutrition exerts considerable effects on health, and dietary interventions are commonly used to treat diseases of metabolic aetiology. Although cancer has a substantial metabolic component1, the principles that define whether nutrition may be used to influence outcomes of cancer are unclear2. Nevertheless, it is established that targeting metabolic pathways with pharmacological agents or radiation can sometimes lead to controlled therapeutic outcomes. By contrast, whether specific dietary interventions can influence the metabolic pathways that are targeted in standard cancer therapies is not known. Here we show that dietary restriction of the essential amino acid methionine—the reduction of which has anti-ageing and anti-obesogenic properties—influences cancer outcome, through controlled and reproducible changes to one-carbon metabolism. This pathway metabolizes methionine and is the target of a variety of cancer interventions that involve chemotherapy and radiation. Methionine restriction produced therapeutic responses in two patient-derived xenograft models of chemotherapy-resistant RAS-driven colorectal cancer, and in a mouse model of autochthonous soft-tissue sarcoma driven by a G12D mutation in KRAS and knockout of p53 (KrasG12D/+;Trp53−/−) that is resistant to radiation. Metabolomics revealed that the therapeutic mechanisms operate via tumour-cell-autonomous effects on flux through one-carbon metabolism that affects redox and nucleotide metabolism—and thus interact with the antimetabolite or radiation intervention. In a controlled and tolerated feeding study in humans, methionine restriction resulted in effects on systemic metabolism that were similar to those obtained in mice. These findings provide evidence that a targeted dietary manipulation can specifically affect tumour-cell metabolism to mediate broad aspects of cancer outcome. In two patient-derived xenograft models of colorectal cancer and a mouse model of autochthonous soft-tissue sarcoma, dietary restriction of methionine influences the outcome of cancer and interacts with antimetabolite and radiation therapies, through effects on one-carbon metabolism.
- Published
- 2019
30. Linking a cell-division gene and a suicide gene to define and improve cell therapy safety
- Author
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Maria V. Shutova, Qin Liang, Claudio Monetti, Kristina Vintersten Nagy, Eric J Neely, Huijuan Yang, Christopher Kim, Sabiha Hacibekiroglu, Istvan Gyongy, Andras Nagy, Maria Mileikovsky, Puzheng Zhang, Hoon Ki Sung, and Chengjin Li
- Subjects
Male ,0301 basic medicine ,Cell ,Cell- and Tissue-Based Therapy ,Bioinformatics ,Thymidine Kinase ,Cell therapy ,Mice ,03 medical and health sciences ,Genome editing ,CDC2 Protein Kinase ,Animals ,Humans ,Simplexvirus ,Medicine ,Induced pluripotent stem cell ,Ganciclovir ,Embryonic Stem Cells ,Cell Proliferation ,Cyclin-dependent kinase 1 ,Multidisciplinary ,Cell growth ,business.industry ,Genes, Transgenic, Suicide ,Suicide gene ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Thymidine kinase ,Female ,Patient Safety ,business ,Cell Division - Abstract
Human pluripotent cell lines hold enormous promise for the development of cell-based therapies. Safety, however, is a crucial prerequisite condition for clinical applications. Numerous groups have attempted to eliminate potentially harmful cells through the use of suicide genes1, but none has quantitatively defined the safety level of transplant therapies. Here, using genome-engineering strategies, we demonstrate the protection of a suicide system from inactivation in dividing cells. We created a transcriptional link between the suicide gene herpes simplex virus thymidine kinase (HSV-TK) and a cell-division gene (CDK1); this combination is designated the safe-cell system. Furthermore, we used a mathematical model to quantify the safety level of the cell therapy as a function of the number of cells that is needed for the therapy and the type of genome editing that is performed. Even with the highly conservative estimates described here, we anticipate that our solution will rapidly accelerate the entry of cell-based medicine into the clinic.
- Published
- 2018
31. The top 100 papers.
- Author
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Van Noorden, Richard, Maher, Brendan, and Nuzzo, Regina
- Subjects
- *
BIBLIOGRAPHICAL citations , *BIBLIOGRAPHICAL citation research , *BIOINFORMATICS , *PHYLOGENY , *RESEARCH , *CHARTS, diagrams, etc. - Abstract
The article discusses the most-cited researches in history. Topics include topics of papers and citations that has allowed them to reach the top the most cited research like Bioinformatics, Phylogenetics and Statistics, a chart showing the top 10 most cited researches and information on the first systematic effort to track citations the Science Citation Index (SCI).
- Published
- 2014
- Full Text
- View/download PDF
32. Genetic mechanisms of critical illness in COVID-19
- Author
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Pairo-Castineira, Erola, Clohisey, Sara, Klaric, Lucija, Bretherick, Andrew D, Rawlik, Konrad, Pasko, Dorota, Walker, Susan, Parkinson, Nick, Fourman, Max Head, Russell, Clark D, Furniss, James, Richmond, Anne, Gountouna, Elvina, Wrobel, Nicola, Harrison, David, Wang, Bo, Yang, Wu, Meynert, Alison, Griffiths, Fiona, Oosthuyzen, Wilna, Kousathanas, Athanasios, Moutsianas, Loukas, Yang, Zhijian, Zhai, Ranran, Zheng, Chenqing, Grimes, Graeme, Beale, Rupert, Millar, Jonathan, Shih, Barbara, Keating, Sean, Zechner, Marie, Haley, Chris, Porteous, David J, Hayward, Caroline, Yang, Jian, Knight, Julian, Summers, Charlotte, Shankar-Hari, Manu, Klenerman, Paul, Turtle, Lance, Antonia, Ho, Moore, Shona C, Hinds, Charles, Horby, Peter, Nichol, Alistair, Maslove, David, Ling, Lowell, Mcauley, Danny, Montgomery, Hugh, Walsh, Timothy, Pereira, Alexandre C, Renieri, Johnny, Millar, Alistair, Nichol, Tim, Walsh, Manu, Shankar-Hari, Chris, Ponting, Jen, Meikle, Paul, Finernan, Ellie, Mcmaster, Andy, Law, J Kenneth Baillie, Trevor, Paterson, Tony, Wackett, Ruth, Armstrong, Richard, Clark, Audrey, Coutts, Lorna, Donnelly, Tammy, Gilchrist, Katarzyna, Hafezi, Louise, Macgillivray, Alan, Maclean, Sarah, Mccafferty, Kirstie, Morrice, Jane, Weaver, Ceilia, Boz, Ailsa, Golightly, Mari, Ward, Hanning, Mal, Helen, Szoor-McElhinney, Adam, Brown, Ross, Hendry, Andrew, Stenhouse, Louise, Cullum, Dawn, Law, Sarah, Law, Rachel, Law, Maaike, Swets, Nicky, Day, Filip, Taneski, Esther, Duncan, Nicholas, Parkinson, Collier, D, Wood, S, Zak, A, Borra, C, Matharu, M, May, P, Alldis, Z, Mitchelmore, O, Bowles, R, Easthope, A, Bibi, F, Lancoma-Malcolm, I, Gurasashvili, J, Pheby, J, Shiel, J, Bolton, M, Patel, M, Taylor, M, Zongo, O, Ebano, P, Harding, P, Astin-Chamberlain, R, Choudhury, Y, Cox, A, Kallon, D, Burton, M, Hall, R, Blowes, S, Prime, Z, Biddle, J, Prysyazhna, O, Newman, T, Tierney, C, Kassam, J, Shankar-Hari, M, Ostermann, M, Campos, S, Bociek, A, Lim, R, Grau, N, O Jones, T, Whitton, C, 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Konrad [0000-0002-0010-370X], Walker, Susan [0000-0002-5016-6426], Fourman, Max Head [0000-0001-7381-2278], Russell, Clark D [0000-0002-9873-8243], Gountouna, Elvina [0000-0001-7870-2780], Wang, Bo [0000-0002-1580-797X], Wu, Yang [0000-0002-0128-7280], Kousathanas, Athanasios [0000-0001-6265-6521], Moutsianas, Loukas [0000-0001-5453-345X], Zhai, Ranran [0000-0002-5834-9120], Beale, Rupert [0000-0002-6705-8560], Keating, Sean [0000-0001-8552-5604], Haley, Chris [0000-0002-9811-0210], Porteous, David J [0000-0003-1249-6106], Hayward, Caroline [0000-0002-9405-9550], Yang, Jian [0000-0003-2001-2474], Knight, Julian [0000-0002-0377-5536], Summers, Charlotte [0000-0002-7269-2873], Shankar-Hari, Manu [0000-0002-5338-2538], Turtle, Lance [0000-0002-0778-1693], Moore, Shona C [0000-0001-8610-2806], Hinds, Charles [0000-0001-5094-8324], McAuley, Danny [0000-0002-3283-1947], Montgomery, Hugh [0000-0001-8797-5019], Renieri, Alessandra [0000-0002-0846-9220], Shen, Xia [0000-0003-4390-1979], 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T., Massey, E., Croston, G., Reschreiter, H., Camsooksai, J., Patch, S., Jenkins, S., Humphrey, C., Wadams, B., Msiska, M., Adanini, O., Attwood, B., Parsons, P., Tatham, K., Jhanji, S., Black, E., Dela Rosa, A., Howle, R., Thomas, B., Bemand, T., Raobaikady, R., Saha, R., Staines, N., Daniel, A., Finn, J., Hutter, J., Doble, P., Shovelton, C., Pawley, C., Kannan, T., Hill, M., Combes, E., Monnery, S., Joefield, T., Popescu, M., Thankachen, M., Oblak, M., Little, J., Mcivor, S., Brady, A., Whittle, H., Prady, H., Chan, R., Ahmed, A., Morris, A., Gibson, C., Gordon, E., Keenan, S., Quinn, H., Benyon, S., Marriott, S., Zitter, L., Park, L., Baines, K., Lyons, M., Holland, M., Keenan, N., Young, M., Garrioch, S., Dawson, J., Tolson, M., Scholefield, B., Bi, R., Richardson, N., Schumacher, N., Cosier, T., Millen, G., Higham, A., Turki, S., Allen, L., Crisp, N., Hazleton, T., Knight, A., Deery, J., Price, C., Turney, S., Tilbey, S., Beranova, E., Wright, D., George, L., Twiss, S., Wadd, S., Postlethwaite, K., Gondo, P., Masunda, B., Kayani, A., Hadebe, B., Whiteside, J., Clarke, N., Donnison, P., Trim, F., Leadbitter, I., Butcher, D., O'Sullivan, S., Purewal, B., Bell, S., Rivers, V., O'Leary, R., Birch, J., Collins, E., Anderson, S., Hammerton, K., Andrews, E., Burns, K., Edmond, I., Todd, A., Donnachie, J., Turner, P., Prentice, L., Symon, L., Runciman, N., Auld, F., Halkes, M., Mercer, P., Thornton, L., Debreceni, G., Wilkins, J., Crickmore, V., Subramanian, G., Marshall, R., Jennings, C., Latif, M., Bunni, L., Spivey, M., Bean, S., Burt, K., Linnett, V., Ritzema, J., Sanderson, A., Mccormick, W., Bokhari, M., Kapoor, R., Loader, D., Ayers, A., Harrison, W., North, J., Belagodu, Z., Paramsothy, R., Olufuwa, O., Gherman, A., Fuller, B., Stuart, C., Kelsall, O., Davis, C., Wild, L., Wood, H., Thrush, J., Durie, A., Austin, K., Archer, K., Anderson, P., Vigurs, C., Thorpe, C., Knights, E., Boyle, N., Price, A., Kubisz-Pudelko, A., Wood, D., Lewis, A., Board, S., Pippard, L., Perry, J., Beesley, K., Rattray, A., Lee, E., Lennon, L., Douglas, K., Bell, D., Boyle, R., Glass, L., Nauman Akhtar, M., Dent, K., Potoczna, D., Pearson, S., Horsley, E., Spencer, S., Mullan, D., Skinner, D., Gaylard, J., Barber, R., Hewitt, C., Hilldrith, A., Shepardson, S., Wills, M., Jackson-Lawrence, K., Gupta, A., Timlick, E., Gorman, C., Otahal, I., Gales, A., Coetzee, S., Sell, C., Raj, M., Peiu, M., Quaid, S., Watson, E., Elliott, K., Mallinson, J., Chandler, B., Turnbull, A., Finch, C., Holl, C., Cooper, J., Evans, A., Khaliq, W., Collins, A., Gude, E. T., Love, N., van Koutrik, L., Hunt, J., Kaye, D., Fisher, E., Brayne, A., Tuckey, V., Jackson, P., Parkin, J., Tariq, A., Houlden, H., Tucci, A., Hardy, J., Moncur, E., Highgate, J., Cowley, A., Mitra, A., Stead, R., Behan, T., Burnett, C., Newton, M., Heeney, E., Pollard, R., Hatton, J., Patel, A., Kasipandian, V., Allibone, S., Genetu, R. M., O'Brien, L., Omar, Z., Perkins, E., Davies, K., Tetla, D., Shelley, B., Irvine, V., Williams, S., Williams, P., Goodsell, J., Tutton, R., Bough, L., Winter-Goodwin, B., Kitson, R., Pinnell, J., Wilson, A., Nortcliffe, T., Wood, T., Home, M., Holdroyd, K., Robinson, M., Shaw, R., Greig, J., Brady, M., Haigh, A., Matupe, L., Usher, M., Mellor, S., Dale, S., Gledhill, L., Shaw, L., Turner, G., Kelly, D., Anwar, B., Riley, H., Sturgeon, H., Ali, A., Thomis, L., Melia, D., Dance, A., Humphreys, S., Frost, I., Gopal, V., Godden, J., Holden, A., Swann, S., Smith, T., Clapham, M., Poultney, U., Harper, R., Rice, P., Reece-Anthony, R., Gurung, B., Moultrie, S., Odam, M., Mayer, A., Bellini, A., Pickard, A., Bryant, J., Roe, N., Sowter, J., Lang, K., Taylor, J., Barry, P., Hobrok, M., Tench, H., Wolf-Roberts, R., Mcguinness, H., Loosley, R., Hawcutt, D., Rad, L., O'Malley, L., Saunderson, P., Seddon, G., Anderson, T., Rogers, N., Ruddy, J., Harkins, M., Beith, C., Mcalpine, A., Ferguson, L., Grant, P., Macfadyen, S., Mclaughlin, M., Baird, T., Rundell, S., Welsh, B., Hamill, R., Fisher, F., Gregory, J., Campbell, A., Smuts, S., Kenneth Baillie, J., Carson, G., Alex, B., Bach, B., Barclay, W. S., Bogaert, D., Chand, M., Cooke, G. S., Docherty, A. B., Dunning, J., da Silva Filipe, A., Fletcher, T., Green, C. A., Harrison, E. M., Hiscox, J. A., Ho, A. Y. W., Horby, P. W., Ijaz, S., Khoo, S., Lim, W. S., Mentzer, A. J., Merson, L., Meynert, A. M., Noursadeghi, M., Palmarini, M., Paxton, W. A., Pollakis, G., Price, N., Rambaut, A., Robertson, D. L., Sancho-Shimizu, V., Scott, J. T., de Silva, T., Sigfrid, L., Solomon, T., Sriskandan, S., Stuart, D., Tedder, R. S., Thomson, E. C., Thompson, A. A. R., Thwaites, R. S., Turtle, L. C. W., Zambon, M., Hardwick, H., Donohue, C., Lyons, R., Norman, L., Pius, R., Drake, T. M., Fairfield, C. J., Knight, S. R., Mclean, K. A., Murphy, D., Shaw, C. A., Dalton, J., Girvan, M., Saviciute, E., Roberts, S., Harrison, J., Marsh, L., Connor, M., Halpin, S., Gamble, C., Leeming, G., Wham, M., Greenhalf, W., Shaw, V., Mcdonald, S., Ganna, A., Sulem, P., van Heel, D. A., Cordioli, M., Sveinbjornsson, G., Niemi, M. E. K., Shelton, J. F., Shastri, A. J., Ye, C., Weldon, C. H., Filshtein-Sonmez, T., Coker, D., Symons, A., Esparza-Gordillo, J., Aslibekyan, S., Auton, A., Krieger, J. E., Marques, E., Jannes, C. E., Mari, F., Daga, S., Baldassarri, M., Benetti, E., Furini, S., Fallerini, C., Fava, F., Valentino, F., Doddato, G., Giliberti, A., Tita, R., Amitrano, S., Bruttini, M., Croci, S., Meloni, I., Pinto, A. M., Frullanti, E., Mencarelli, M. A., Rizzo, C. L., Montagnani, F., Di Sarno, L., Tommasi, A., Palmieri, M., Emiliozzi, A., Fabbiani, M., Rossetti, B., Zanelli, G., Bargagli, E., Bergantini, L., D'Alessandro, M., Cameli, P., Bennet, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, F., Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Spertilli, C., Feri, M., Donati, A., Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Spagnesi, M., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Ognibene, A., Vaghi, M., D'Arminio Monforte, A., Merlini, E., Mondelli, M. U., Mantovani, S., Ludovisi, S., Girardis, M., Venturelli, S., Sita, M., Cossarizza, A., Antinori, A., Vergori, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, M. E., Magro, P., Zanella, I., Della Monica, M., Piscopo, C., Capasso, M., Russo, R., Andolfo, I., Iolascon, A., Fiorentino, G., Carella, M., Castori, M., Merla, G., Aucella, F., Raggi, P., Marciano, C., Perna, R., Bassetti, M., Di Biagio, A., Sanguinetti, M., Masucci, L., Valente, S., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Baratti, S., Trotta, T., Giannattasio, F., Coiro, G., Lena, F., Coviello, D. A., Mussini, C., Bosio, G., Martinelli, E., Mancarella, S., Tavecchia, L., Crotti, L., Picchiotti, N., Gori, M., Gabbi, C., Sanarico, M., Ceri, S., Pinoli, P., Raimondi, F., Biscarini, F., Stella, A., Shen, X., Ponting, C. P., Fawkes, A., Tenesa, A., Caulfield, M., Scott, R., Rowan, K., Murphy, L., Openshaw, P. J. M., Semple, M. G., Vitart, V., and Wilson, J. F.
- Subjects
0301 basic medicine ,Male ,CCR2 ,Chromosomes, Human, Pair 21 ,Genome-wide association study ,Receptor, Interferon alpha-beta ,Disease ,Bioinformatics ,Genome-wide association studies ,23andMe Investigators ,Interferon alpha-beta ,0302 clinical medicine ,Receptors ,2',5'-Oligoadenylate Synthetase ,Pair 12 ,genetics ,Lung ,BRACOVID Investigators ,Multidisciplinary ,GenOMICC Investigators ,Tyrosine kinase 2 ,030220 oncology & carcinogenesis ,Multigene Family ,Medical genetics ,Female ,Dipeptidyl-Peptidases and Tripeptidyl-Peptidase ,5'-Oligoadenylate Synthetase ,Human ,Receptor ,medicine.medical_specialty ,Critical Care ,Receptors, CCR2 ,General Science & Technology ,Critical Illness ,Chromosomes ,03 medical and health sciences ,Intensive care ,Mendelian randomization ,Immunogenetics ,medicine ,Humans ,Dipeptidyl-Peptidases and Tripeptidyl-Peptidases ,Gen-COVID Investigators ,Inflammation ,TYK2 Kinase ,Chromosomes, Human, Pair 12 ,Pair 19 ,SARS-CoV-2 ,business.industry ,Drug Repositioning ,COVID-19 ,United Kingdom ,COVID-19 Human Genetics Initiative ,030104 developmental biology ,Viral infection ,Chromosomes, Human, Pair 19 ,Genome-Wide Association Study ,Pharmacogenomics ,ISARICC Investigators ,Pair 21 ,2' ,business - Abstract
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079,P=1.65×10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1,OAS2andOAS3); on chromosome 19p13.2 (rs74956615,P=2.3×10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069,P=3.98× 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757,P=4.99×10−8) in the interferon receptor geneIFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression ofIFNAR2, or high expression ofTYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptorCCR2is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice.
- Published
- 2020
- Full Text
- View/download PDF
33. Cells or drugs? The race to regenerate the heart
- Author
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Benjamin Plackett
- Subjects
0301 basic medicine ,03 medical and health sciences ,Race (biology) ,030104 developmental biology ,0302 clinical medicine ,Multidisciplinary ,business.industry ,Scar tissue ,Medicine ,030204 cardiovascular system & hematology ,Stem cell ,Bioinformatics ,business - Abstract
Researchers are debating how to convince the heart to heal itself instead of laying down scar tissue after a heart attack. Researchers are debating how to convince the heart to heal itself instead of laying down scar tissue after a heart attack.
- Published
- 2021
34. Genetics of rheumatoid arthritis contributes to biology and drug discovery.
- Author
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Okada, Yukinori, Wu, Di, Trynka, Gosia, Raj, Towfique, Terao, Chikashi, Ikari, Katsunori, Kochi, Yuta, Ohmura, Koichiro, Suzuki, Akari, Yoshida, Shinji, Graham, Robert R., Manoharan, Arun, Ortmann, Ward, Bhangale, Tushar, Denny, Joshua C., Carroll, Robert J., Eyler, Anne E., Greenberg, Jeffrey D., Kremer, Joel M., and Pappas, Dimitrios A.
- Subjects
- *
RHEUMATOID arthritis , *HUMAN genetics , *BIOLOGICAL databases , *BIOINFORMATICS , *SOMATIC mutation , *GENETIC polymorphisms - Abstract
A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ∼10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2, 3, 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
35. Temprian Therapeutics: developing a gene-based treatment for vitiligo
- Author
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Charles Schmidt
- Subjects
0301 basic medicine ,Multidisciplinary ,integumentary system ,business.industry ,Drug discovery ,fungi ,food and beverages ,Vitiligo ,Bioinformatics ,medicine.disease ,behavioral disciplines and activities ,humanities ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Medicine ,Stem cell ,business ,Gene - Abstract
A modified protein to disrupt the autoimmune cascade that can lead to the skin-pigment condition makes the company a finalist for The Spinoff Prize. A modified protein to disrupt the autoimmune cascade that can lead to the skin-pigment condition makes the company a finalist for The Spinoff Prize.
- Published
- 2020
36. EraCal Therapeutics: a new drug candidate for obesity
- Author
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Elie Dolgin
- Subjects
0303 health sciences ,03 medical and health sciences ,Multidisciplinary ,business.industry ,Drug candidate ,Drug discovery ,Medicine ,02 engineering and technology ,021001 nanoscience & nanotechnology ,0210 nano-technology ,business ,Bioinformatics ,030304 developmental biology - Abstract
The start-up that developed the compound is a finalist for The Spinoff Prize. The start-up that developed the compound is a finalist for The Spinoff Prize.
- Published
- 2020
37. Forkhead BioTherapeutics: developing a diabetes pill
- Author
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Eric Bender
- Subjects
Drug ,0303 health sciences ,Multidisciplinary ,business.industry ,Drug discovery ,Insulin ,medicine.medical_treatment ,media_common.quotation_subject ,MEDLINE ,Disease ,Bioinformatics ,medicine.disease ,behavioral disciplines and activities ,humanities ,03 medical and health sciences ,0302 clinical medicine ,Pill ,Diabetes mellitus ,Medicine ,business ,psychological phenomena and processes ,030217 neurology & neurosurgery ,030304 developmental biology ,media_common - Abstract
The drug, which could restart insulin production in people with the disease, is made by one of the finalists of The Spinoff Prize. The drug, which could restart insulin production in people with the disease, is made by one of the finalists of The Spinoff Prize.
- Published
- 2020
38. A race to determine what drives COVID-19 severity
- Author
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Marios Koutsakos and Katherine Kedzierska
- Subjects
0301 basic medicine ,Multidisciplinary ,Coronavirus disease 2019 (COVID-19) ,biology ,business.industry ,viruses ,030208 emergency & critical care medicine ,Host factors ,Medical research ,Bioinformatics ,medicine.disease_cause ,biology.organism_classification ,Affect (psychology) ,03 medical and health sciences ,Race (biology) ,030104 developmental biology ,0302 clinical medicine ,Pandemic ,medicine ,business ,Betacoronavirus ,Coronavirus - Abstract
Efforts are ongoing to find which human or viral factors underpin whether a person with COVID-19 will develop severe symptoms. Clinical evidence linked to two viral lineages now provides key insights into this enigma. Clinical evidence reveals how host factors affect coronavirus infection.
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- 2020
- Full Text
- View/download PDF
39. Conflicting evidence for HIV enrichment in CD32+ CD4 T cells
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Ann Thorkelson, Eli Boritz, Ashley T. Haase, Jodi Anderson, Susan Moir, Liliana Pérez, Timothy W. Schacker, Jeffrey G. Chipman, Daniel C. Douek, and Tae Wook Chun
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,Multidisciplinary ,Text mining ,business.industry ,Human immunodeficiency virus (HIV) ,medicine ,MEDLINE ,Biology ,medicine.disease_cause ,business ,Bioinformatics - Published
- 2018
40. The amyloid hypothesis on trial
- Author
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Simon Makin
- Subjects
0301 basic medicine ,Amyloid pathology ,Plaque, Amyloid ,tau Proteins ,Disease ,Protein aggregation ,Bioinformatics ,Antiviral Agents ,Models, Biological ,Protein Aggregation, Pathological ,Treatment failure ,Mice ,03 medical and health sciences ,Apolipoproteins E ,0302 clinical medicine ,Alzheimer Disease ,medicine ,Animals ,Humans ,Treatment Failure ,Pathological ,Aged ,Amyloid beta-Peptides ,Multidisciplinary ,business.industry ,Neurodegeneration ,Disease progression ,Reproducibility of Results ,medicine.disease ,Anti-Bacterial Agents ,Biochemistry of Alzheimer's disease ,030104 developmental biology ,Disease Progression ,business ,030217 neurology & neurosurgery - Abstract
As the development of treatments for Alzheimer’s disease continues to stumble, is it time for researchers to broaden their list of the condition’s potential causes? As the development of treatments for Alzheimer’s disease continues to stumble, is it time for researchers to broaden their list of the condition’s potential causes?
- Published
- 2018
41. DNA methylation-based classification of central nervous system tumours
- Author
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Till Milde, Matija Snuderl, Martin Bendszus, Ralf Ketter, Catherine Keohane, Marco Prinz, Katja von Hoff, Aristotelis Tsirigos, Hildegard Dohmen, Manfred Westphal, Ute Pohl, Gabriele Schackert, Christian Koelsche, Eleonora Aronica, Bernhard Radlwimmer, Bjarne Winther Kristensen, Martin Hasselblatt, David T.W. Jones, Christian Mawrin, Dominik Sturm, Patricia Kohlhof, Peter Lichter, Annekathrin Kratz, Anne K. Braczynski, Helmut Mühleisen, Wolf Mueller, Wolfgang Brück, Stephan Frank, Andreas Unterberg, Michael Weller, Matthias A. Karajannis, Astrid Gnekow, Lukas Chavez, Andreas E. Kulozik, Christoph Geisenberger, Christine Haberler, Ori Staszewski, Amar Gajjar, Stephanie Rozsnoki, Mélanie Pagès, Olaf Witt, Paul A. Northcott, Matt Lechner, Thomas S. Jacques, Martina Deckert, Axel Benner, Jordan R. Hansford, Ingmar Blümcke, Marina Ryzhova, Gudrun Fleischhack, Jonathan Serrano, Jens Schittenhelm, Martin Sill, Sebastian Brandner, Stephan Tippelt, Dietmar R. Lohmann, Hermann L. Müller, Petra Temming, Nils W. Engel, Khalida Wani, Pablo Hernáiz Driever, Christel Herold-Mende, David W. Ellison, Arie Perry, Michael C. Frühwald, Stefan M. Pfister, Christof M. Kramm, Stefanie Brehmer, Daniel Hänggi, Jane Cryan, Torsten Pietsch, Wolfram Scheurlen, Marcel Seiz-Rosenhagen, Volkmar Hans, Adriana Olar, Werner Paulus, Chris Jones, Annie Huang, Patrick N. Harter, Felice Giangaspero, Marcel Kool, Kenneth Aldape, Marco Gessi, Silvia Hofer, Fausto J. Rodriguez, Anne Jouvet, Roland Coras, Annika K. Wefers, Leonille Schweizer, Vincent Peter Collins, Beatriz Lopes, Rolf Bjerkvig, Matthias Schick, Michel Mittelbronn, Andrey Korshunov, Johannes Schramm, Marc Zapatka, Annett Hölsken, Michael Platten, Kerstin Lindenberg, Jürgen Debus, Christian Hartmann, Ekkehard Hewer, Pascale Varlet, Melanie Bewerunge-Hudler, Till Acker, Matthias Preusser, Elisabeth J. Rushing, Michael A. Farrell, Kristian W. Pajtler, Nada Jabado, Kasthuri Kannan, Wolfgang Wick, David E. Reuss, Rolf Buslei, Nicholas G. Gottardo, Giles W. Robinson, Stefan Rutkowski, Jürgen Hench, Andreas von Deimling, Ulrich Schüller, Zane Jaunmuktane, Pieter Wesseling, Hendrik Witt, Albert J. Becker, Frank L. Heppner, Roger Fischer, Ziad Khatib, Guido Reifenberger, Arend Koch, Gabriele Calaminus, Karl H. Plate, Volker Hovestadt, Michael D. Taylor, Camelia-Maria Monoranu, Damian Stichel, Felix Sahm, Kristin Huang, David Capper, Florian Selt, Daniel Schrimpf, Rudi Beschorner, Boyan K. Garvalov, Pathology, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Systems & Network Neuroscience, CCA - Imaging and biomarkers, APH - Mental Health, ANS - Cellular & Molecular Mechanisms, and APH - Aging & Later Life
- Subjects
Adult ,Male ,0301 basic medicine ,Adolescent ,DNA methylation-based classification ,Central nervous system ,Medizin ,Bioinformatics ,CNS cancer ,Central Nervous System Neoplasms ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Age groups ,central nervous system tumours ,pathological diagnosis ,cancer ,Humans ,Medicine ,Central Nervous System Neoplasms/classification ,General ,Child ,Aged ,Aged, 80 and over ,Multidisciplinary ,business.industry ,Extramural ,Infant ,Reproducibility of Results ,DNA Methylation ,Middle Aged ,Standard methods ,Optimal management ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Child, Preschool ,DNA methylation ,Female ,DNA microarray ,business ,030217 neurology & neurosurgery ,Unsupervised Machine Learning - Abstract
Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging - with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
- Published
- 2018
42. C ellular censuses to guide cancer care
- Author
-
Michael Eisenstein
- Subjects
0303 health sciences ,Multidisciplinary ,business.industry ,medicine.medical_treatment ,Cancer ,Genomics ,Immunotherapy ,Bioinformatics ,Proteomics ,medicine.disease ,Disease course ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,030220 oncology & carcinogenesis ,medicine ,business ,030304 developmental biology - Abstract
In the age of immunotherapy, cancer biologists are relying on a new generation of tools to learn how the interplay between tumours and immune cells shapes the course of disease. In the age of immunotherapy, cancer biologists are relying on a new generation of tools to learn how the interplay between tumours and immune cells shapes the course of disease.
- Published
- 2019
43. Protein-slaying drugs could be the next blockbuster therapies
- Author
-
Megan Scudellari
- Subjects
0303 health sciences ,Multidisciplinary ,010405 organic chemistry ,Drug discovery ,business.industry ,viruses ,biochemical phenomena, metabolism, and nutrition ,Bioinformatics ,01 natural sciences ,0104 chemical sciences ,03 medical and health sciences ,Medicine ,business ,030304 developmental biology - Abstract
Researchers are hijacking the cell’s protein-disposal system in the fight against Alzheimer’s and intractable cancers. Researchers are hijacking the cell’s protein-disposal system in the fight against Alzheimer’s and intractable cancers.
- Published
- 2019
44. The next 20 years of human genomics must be more equitable and more open.
- Abstract
By re-committing to data sharing, researchers can fulfil the long-delayed promise of the Human Genome Project. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
45. Network control principles predict neuron function in the Caenorhabditis elegans connectome
- Author
-
Emma K. Towlson, Gang Yan, Yee Lian Chew, Petra E. Vértes, Albert-László Barabási, Denise S. Walker, William R Schafer, Vertes, Petra [0000-0002-0992-3210], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Nematode caenorhabditis elegans ,Biology ,Bioinformatics ,Article ,03 medical and health sciences ,0302 clinical medicine ,Experimental proof ,Connectome ,medicine ,Animals ,Caenorhabditis elegans ,Motor Neurons ,Neurons ,Network control ,Multidisciplinary ,Lasers ,biology.organism_classification ,3. Good health ,Controllability ,030104 developmental biology ,medicine.anatomical_structure ,Neuron ,Nerve Net ,Neuroscience ,Locomotion ,030217 neurology & neurosurgery ,Function (biology) - Abstract
Recent studies on the controllability of complex systems offer a powerful mathematical framework to systematically explore the structure-function relationship in biological, social, and technological networks. Despite theoretical advances, we lack direct experimental proof of the validity of these widely used control principles. Here we fill this gap by applying a control framework to the connectome of the nematode Caenorhabditis elegans, allowing us to predict the involvement of each C. elegans neuron in locomotor behaviours. We predict that control of the muscles or motor neurons requires 12 neuronal classes, which include neuronal groups previously implicated in locomotion by laser ablation, as well as one previously uncharacterized neuron, PDB. We validate this prediction experimentally, finding that the ablation of PDB leads to a significant loss of dorsoventral polarity in large body bends. Importantly, control principles also allow us to investigate the involvement of individual neurons within each neuronal class. For example, we predict that, within the class of DD motor neurons, only three (DD04, DD05, or DD06) should affect locomotion when ablated individually. This prediction is also confirmed; single cell ablations of DD04 or DD05 specifically affect posterior body movements, whereas ablations of DD02 or DD03 do not. Our predictions are robust to deletions of weak connections, missing connections, and rewired connections in the current connectome, indicating the potential applicability of this analytical framework to larger and less well-characterized connectomes.
- Published
- 2017
46. Regulating the gene-therapy revolution
- Author
-
Eric Bender
- Subjects
Male ,0301 basic medicine ,Clinical Trials as Topic ,Multidisciplinary ,business.industry ,Drug discovery ,Genetic enhancement ,Genetic Vectors ,Gene Transfer Techniques ,Genetic Therapy ,Dependovirus ,030105 genetics & heredity ,Bioinformatics ,03 medical and health sciences ,Organ Specificity ,Practice Guidelines as Topic ,Government Regulation ,Humans ,Medicine ,Child ,business ,human activities ,Gene - Abstract
The medical regulatory authorities ride a wave of clinical studies for gene therapies. The medical regulatory authorities ride a wave of clinical studies for gene therapies.
- Published
- 2018
47. Staring into the human genome to diagnose COVID.
- Author
-
Noronha, Patricia Maia
- Abstract
Bioinformatician Lucía Spangenberg is helping to make genetic sequencing available to anyone who needs it. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
48. Gut feeling: building a picture of Latin American microbiomes.
- Author
-
Leeming, Jack
- Abstract
Computational microbiologist Gregorio Iraola leads a consortium focused on tailoring public-health interventions for local needs. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
49. Sickle-cell disease
- Author
-
Herb Brody
- Subjects
Multidisciplinary ,business.industry ,Genetic enhancement ,African descent ,Medicine ,Disease ,business ,Bioinformatics - Abstract
A condition that affects many people of African descent is finally meeting its therapeutic match. A condition that affects many people of African descent is finally meeting its therapeutic match.
- Published
- 2021
50. Africa needs more bioinformaticians for population studies.
- Author
-
Akintola AA, Hwang UW, and Aborode AT
- Subjects
- Africa epidemiology, Research Design, Computational Biology, Genomics
- Published
- 2022
- Full Text
- View/download PDF
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