Intended for a mixed/general audience of Clinicians, Business Interests, and Research Scientists. No audio, however the event was recorded and posted to youtube by Genome Atlantic: http://www.youtube.com/watch?v=FLVjwOngu-Q I
Plasmodium CSP - Based vaccines Past - prsesent - future - Conférence de la 6e édition du Cours international « Atelier Paludisme » - SNOUNOU Georges - Singapour - snounou@mnhn.fr
genetic engineering: Genetic engineering, also called genetic modification, is the direct manipulation of an organism's genome using biotechnology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. Many organism are manipulated with the help genetic engineering useful for mankind.
What are an expression vector? Detailed description of plant gene structure. Plant expression vector systems are generally consists of Ri and Ti plasmids.
The other vectors which are generally used are DNA and RNA viruses.
A transplastomic plant is a genetically modified plant in which the new genes have not been inserted in the nuclear DNA but in the DNA of the chloroplasts.
Plasmodium CSP - Based vaccines Past - prsesent - future - Conférence de la 6e édition du Cours international « Atelier Paludisme » - SNOUNOU Georges - Singapour - snounou@mnhn.fr
genetic engineering: Genetic engineering, also called genetic modification, is the direct manipulation of an organism's genome using biotechnology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. Many organism are manipulated with the help genetic engineering useful for mankind.
What are an expression vector? Detailed description of plant gene structure. Plant expression vector systems are generally consists of Ri and Ti plasmids.
The other vectors which are generally used are DNA and RNA viruses.
A transplastomic plant is a genetically modified plant in which the new genes have not been inserted in the nuclear DNA but in the DNA of the chloroplasts.
Presentation at the Canadian Cancer Research Conference satellite bioinformatics.ca workshop. This one is an introduction to tcga, icgc and cosmic databases.
We isolated and analyzed, at single-nucleotide resolution, cancer-associated neochromosomes from well- and/or dedifferentiated liposarcomas. Neochromosomes, which can exceed 600 Mb in size, initially arise as circular structures following chromothripsis involving chromosome 12. The core of the neochromosome is amplified, rearranged, and corroded through hundreds of breakage-fusion-bridge cycles. Under selective pressure, amplified oncogenes are overexpressed, while coamplified passenger genes may be silenced epigenetically. New material may be captured during punctuated chromothriptic events. Centromeric corro- sion leads to crisis, which is resolved through neocentromere formation or native centromere capture. Finally, amplification terminates, and the neochromosome core is stabilized in linear form by telomere capture. This study investigates the dynamic mutational processes underlying the life history of a special form of cancer mutation.
"Introns: Structure and Functions" during November, 2011 (Friday Seminar activity, Department of Biotechnology, University of Agricultural Sciences, Dharwad, Karnataka) by Yogesh S Bhagat (Ph D Scholar)
Personalized Medicine and the Omics Revolution by Professor Mike SnyderThe Hive
Personalized medicine is expected to benefit from the combination of genomic information with the global monitoring of molecular components and physiological states. To ascertain whether this can be achieved, we determined the whole genome sequence of an individual at high accuracy and performed an integrated Personal Omics Profiling (iPOP) analysis, combining genomic, transcriptomic, proteomic, metabolomic, and autoantibodyomic information, over a 38-month period that included healthy and two virally infected states. Our iPOP analysis of blood components revealed extensive, dynamic and broad changes in diverse molecular components and biological pathways across healthy and disease conditions. Importantly, genomic information was also used to estimate medical risks, including Type 2 Diabetes, whose onset was observed during the course of our study. Our study demonstrates that longitudinal personal omics profiling can relate genomic information to global functional omics activity for physiological and medical interpretation of healthy and disease states.
Meet the speaker, Professor Michael Snyder (Stanford):
Michael Snyder is the Stanford Ascherman Professor, Chair of Genetics and the Director of the Center of Genomics and Personalized Medicine. He received his Ph.D. from the California Institute of Technology and postdoctoral training at Stanford University. He is a leader in the field of functional genomics and proteomics, and one of the major participants of the ENCODE project. His laboratory study was the first to perform a large-scale functional genomics project in any organism, and has launched many technologies in genomics and proteomics. These including the development of proteome chips, high resolution tiling arrays for the entire human genome, methods for global mapping of transcription factor binding sites (ChIP-chip now replaced by ChIP-seq), paired end sequencing for mapping of structural variation in eukaryotes, de novo genome sequencing of genomes using high throughput technologies and RNA-Seq. These technologies have been used for characterizing genomes, proteomes and regulatory networks. Seminal findings from the Snyder laboratory include; the discovery that much more of the human genome is transcribed and contains regulatory information than was previously appreciated, and a high diversity of transcription factor binding occurs both between and within species. He has also combined different state-of–the-art omics technologies to perform the first longitudinal detailed integrative personal omics profile (iPOP) of person and used this to assess disease risk and monitor disease states for personalized medicine. He is a co-founder of several biotechnology companies including; Protometrix (now part of Life Technologies), Affomix (now part of Illumina), Excelix, and Personalis, and he presently serves on the board of a number of companies.
Epstein-Barr virus genetic variants are associated with multiple sclerosis.Mutiple Sclerosis
Rosella Mechelli, Caterina Manzari, Claudia Policano, Anita Annese, Ernesto Picardi, Renato Umeton, Arianna Fornasiero, Anna Maria D’Erchia, Maria Chiara Buscarinu, Cristina Agliardi, Viviana Annibali, Barbara Serafini, Barbara Rosicarelli, Silvia Romano, Daniela F. Angelini, Vito A.G. Ricigliano, Fabio Buttari, Luca Battistini, Diego Centonze, Franca R. Guerini, Sandra D’Alfonso, Graziano Pesole, Marco Salvetti, Giovanni Ristori
OBJECTIVE:
We analyzed the Epstein-Barr nuclear antigen 2 (EBNA2) gene, which contains the most variable region of the viral genome, in persons with multiple sclerosis (MS) and control subjects to verify whether virus genetic variants are involved in disease development.
METHODS:
A seminested PCR approach and Sanger sequencing were used to analyze EBNA2 in 53 patients and 38 matched healthy donors (HDs). High-throughput sequencing by Illumina MiSeq was also applied in a subgroup of donors (17 patients and 17 HDs). Patients underwent gadolinium-enhanced MRI and human leucocyte antigen typing.
RESULTS:
MS risk significantly correlated with an excess of 1.2 allele (odds ratio [OR] = 5.13; 95% confidence interval [CI] 1.84-14.32; p = 0.016) and underrepresentation of 1.3B allele (OR = 0.23; 95% CI 0.08-0.51; p = 0.0006). We identified new genetic variants, mostly 1.2 allele- and MS-associated (especially amino acid variation at position 245; OR = 9.4; 95% CI 1.19-78.72; p = 0.0123). In all cases, the consensus sequence from deep sequencing confirmed Sanger sequencing (including the cosegregation of newly identified variants with known EBNA2 alleles) and showed that the extent of genotype intraindividual variability was higher than expected: rare EBNA2 variants were detected in all HDs and patients with MS (range 1-17 and 3-19, respectively). EBNA2 variants did not seem to correlate with human leucocyte antigen typing or clinical/MRI features.
CONCLUSIONS:
Our study unveils a strong association between Epstein-Barr virus genomic variants and MS, reinforcing the idea that Epstein-Barr virus contributes to disease development.
Los días 11 y 12 de diciembre de 2014, la Fundación Ramón Areces celebró el Simposio Internacional 'Neuropatías periféricas hereditarias. Desde la biología a la terapéutica' en colaboración con CIBERER-ISCIII y el Centro de Investigación Príncipe Felipe. El tipo más común de estas patologías es la enfermedad de Charcot-Marie-Tooth, un trastorno neuromuscular hereditario con una prevalencia estimada de 17-40 afectados por 100.000 habitantes. Durante estos dos días, investigadores mostraron sus avances en la mejora del diagnóstico y el tratamiento y, por ende, de la aproximación clínica y la calidad de vida de las personas afectadas por estas patologías.
Conferencia de la Dra. Ana María Roa, Bióloga Molecular, sobre Epigenética, impartida en la Universidad Popular Carmen de Michelena de Tres Cantos el 1 de marzo de 2013.
Más información en:
http://www.universidadpopularc3c.es/index.php/actividades/conferencias/event/448-conferencia-una-revision-de-los-conocimientos-fundamentales-de-la-biologia-de-la-celula-la-epigenetica
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists
Bioinformatics in Gene Research
1. Bioinformatics in Genetics
Research
Genetics Noon Symposium Series
Daniel Gaston, PhD
Dr. Karen Bedard Lab, Department of Pathology
November 21st, 2012
2. IGNITE
Orphan Diseases: Identifying Genes and Novel
Therapeutics to Enhance Treatment
Identify causative genetic variations in orphan
diseases with an emphasis on Atlantic Canada
Develop animal and cell culture models
Identify and develop novel therapeutics
igniteproject.ca
3. IGNITE
Orphan Diseases: Identifying Genes and Novel
Therapeutics to Enhance Treatment
Identify causative genetic variations in orphan
diseases with an emphasis on Atlantic Canada
Develop animal and cell culture models
Identify and develop novel therapeutics
igniteproject.ca
4. Outline
Introduction
Bioinformatics in Disease Genomics
Next-Generation Sequencing
Genomics in Research and the Clinic
The Data Deluge and its Solutions
Bioinformatic Methods for Analyzing Genomic Data
Case Studies
Conclusion
5. Bioinformatics in Disease Genomics
Handling and long-term storage of raw data
(sequencing, gene expression, etc)
Maintenance and support of computational
infrastructure
Experimental design
Data analysis
Methods development
Analysis pipelines
Statistical analyses
Algorithm design
6. Bioinformatics in Disease Genomics
Handling and long-term storage of raw data
(sequencing, gene expression, etc)
Maintenance and support of computational
infrastructure
Experimental design
Data analysis
Methods development
Analysis pipelines
Statistical analysis techniques
Algorithm design
9. Disease Genomics: Hunting Down Pathogenic
Genetic Variation
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15. Disease Genomics: Research vs Clinic
Still predominantly research oriented
Complex/Common disease
Mendelian disorders
Cancer genomics
16. Disease Genomics: Research vs Clinic
Still predominantly research oriented
Complex/Common disease
Mendelian disorders
Cancer genomics
Clinical genomics starting to gain traction
Cancer genomics
Cancer subtype identification
Personalized medicine and predicting outcomes
Mendelian disorders
Early diagnosis
Cost effectiveness
17. Clinical Genomics
Children’s Mercy Hospital NICU
In the US >20% of infant deaths due to genetic disease
Serial sequencing of candidate genes too slow
18. Children’s Mercy Hospital NICU
50-hour differential diagnosis of monogenic disease
Sample preparation and sequencing: 30.5 hours
Automated bioinformatics analysis: 17.5 hours
Previous high-throughput sequencing methods: 19 days
Test on seven infants, two previously diagnosed using
standard methods, five undiagnosed
19. Children’s Mercy Hospital NICU
50-hour differential diagnosis of monogenic disease
Sample preparation and sequencing: 30.5 hours
Automated bioinformatics analysis: 17.5 hours
Previous high-throughput sequencing methods: 19 days
Test on seven infants, two previously diagnosed using
standard methods, five undiagnosed
Caveats
Bioinformatics portion not available outside of hospital
Requires thorough clinical phenotyping using a controlled
vocabulary
Generates a large amount of data
20. The Data Deluge
4 million genetic variants
2 million associated with
protein-coding genes
10,000 possibly
of disease
causing type
1500 <1%
frequency in
population
22. Exome Sequencing
Exome: Portion of genome composed of protein-
coding exons and functional RNA sequences
1.5 - 2% of human genome (50 Mb)
> 85% of monogenic diseases due to variants in
exome
Complete exome sequencing: ~ $1000/sample
23. Caveats
Incomplete and non-uniform coverage of exome
Systematic bias (GC content)
Random sampling
Not all genetic variants amenable to discovery
Non-coding variants
Structural variants
26. It Sounds simple but…
For every stage there are multiple programs
available and published in the literature
27. It Sounds simple but…
For every stage there are multiple programs
available and published in the literature
For every program there are a wide-variety of
parameter values and options. Defaults often “good
enough” but not always
28. It Sounds simple but…
For every stage there are multiple programs
available and published in the literature
For every program there are a wide-variety of
parameter values and options. Defaults often “good
enough” but not always
Best combinations of programs and options not well
understood
29. It Sounds simple but…
For every stage there are multiple programs
available and published in the literature
For every program there are a wide-variety of
parameter values and options. Defaults often “good
enough” but not always
Best combinations of programs and options not well
understood
Protocols changing rapidly as new technologies and
methods developed
30. It Sounds simple but…
For every stage there are multiple programs
available and published in the literature
For every program there are a wide-variety of
parameter values and options. Defaults often “good
enough” but not always
Best combinations of programs and options not well
understood
Protocols changing rapidly as new technologies and
methods developed
Different centres and groups use slightly different
workflows with similar, but not identical results
33. If a problem cannot be
solved, enlarge it.
--Dwight D.
Eisenhower
34. Annotations Associated with Genomic
Variants
Is variant in a known protein-coding gene?
What does the gene do?
What molecular pathways?
What protein-protein interactions? 4 million genetic variants
What tissues is it expressed in? 2 million associated with
protein-coding genes
When in development?
10,000 possibly
Has this variant been seen before? of disease
causing type
1500 <1%
What population(s)? With what frequency? frequency in
population
Has it been seen in local sequencing projects?
Is there any known clinical significance?
What is the effect of the variation?
Does it change the resulting protein? How?
37. Potential Pitfalls with Annotation Sources
Databases often overlap and agree, but there may
be disagreements
Source of information: Predicted versus
experimental
Incorrect and out-of-date information
Large-scale un-validated versus manually curated
datasets
39. IGNITE Data Pipeline and Integration
Gene
Annotations Annotated
Genomic
Variants
Mapped Gene
Region(s) Definitions
Filter
Sort
Prioritize
Known Genes Pathway and
Interactions
40. Filtering the Data: Categorization
4 million
variants
Intronic Exonic Intergenic
Amino Acid
Unknown Splice Site Silent Mutation Splice Site
Changing
Potential Potential
Disease Disease
Causing Causing
Known Genetic Amino Acid Amino Acid Known
Stop Loss /
Disease Change Likely Change Likely Polymorphism
Stop Gain
Variant Pathogenic Benign in Population
41. Filtering the Data: Common or Rare?
Variants in dbSNP – Typically known polymorphisms,
unlikely to be associated with rare disease
Variants with relatively high frequency in control
populations (1000 Genomes, HapMAP, EVS, 2800
Exomes)
Number of times variant previously seen at
sequencing centre/locally
42. Notes on Filtering and Variant Annotation
Very important to be aware of population when
referencing frequency of a variant. Incorrect
background leads to incorrect assumptions on
prevalence
43. Notes on Filtering and Variant Annotation
Very important to be aware of population when
referencing frequency of a variant. Incorrect
background leads to incorrect assumptions on
prevalence
Reasonably well-sampled local populations are
better than any other reference
44. Notes on Filtering and Variant Annotation
Very important to be aware of population when
referencing frequency of a variant. Incorrect
background leads to incorrect assumptions on
prevalence
Reasonably well-sampled local populations are
better than any other reference
Strike a balance between hard filtering for variants of
largest potential effect and being inclusive to not
miss variants
45. Notes on Filtering and Variant Annotation
Very important to be aware of population when
referencing frequency of a variant. Incorrect
background leads to incorrect assumptions on
prevalence
Reasonably well-sampled local populations are
better than any other reference
Strike a balance between hard filtering for variants of
largest potential effect and being inclusive to not
miss variants
Some genes acquire large effect variants (stop loss /
stop gain, etc) frequently. Some genes can be lost
without causing disease
55. Conclusions
Bioinformatics is involved at every stage of genomic
research from experimental design through to final
analysis
Standards and best practices do exist, but are
rapidly evolving as new technologies and methods
are developed
Progress towards automatic generation of clinically
interpretable genomics studies
Annotation, filtering, and prioritization of genetic
variants crucial
Balance between false positive calls and false
negatives
56. Where Are We Headed?
Integration of more data sources
Gene expression
More annotation sources
Controlled phenotype vocabularies
Gene Ontology terms
Predictive models
Recessive versus Dominant inheritance and Penetrance
“New” and Emerging Technologies
RNA-Seq (Gene Expression)
ChIP-Seq (Protein-DNA binding)
Single-Molecule Sequencing
57. Acknowledgements
Dalhousie University McGill/Genome Quebec
Dr. Karen Bedard Dr. Jacek Majewski
Dr. Chris McMaster Jeremy
Dr. Andrew Orr Schwartzentruber
Dr. Conrad Fernandez
Dr. Marissa Leblanc Dr. Sarah Dyack
Mat Nightingale Dr. Johane Robataille
Bedard Lab
Genome Atlantic
IGNITE