Presentation by Valerie Schneider discussing Genome Reference Consortium (GRC) plans for the mouse and zebrafish reference genome assemblies, presented at the 2016 meeting of the The Allied Genetic Conference (TAGC). Includes description of resources at the National Center for Biotechnology Information (NCBI) for working with reference genome assemblies.
Genomics is the study of an organism's entire genome, which is the complete set of genetic material present in its DNA. This includes all the genes, non-coding regions, and regulatory sequences. Genomics involves sequencing and analyzing the DNA to identify genes, variations (such as single nucleotide polymorphisms or SNPs), and other structural features of the genome.
Accelerating the benefits of genomics worldwideJoaquin Dopazo
Grand Challenges in Genomics
A Joint NHGRI and Wellcome Trust Strategic Meeting
25 and 26 February 2019
https://www.wellcomeevents.org/WELLCOME/media/uploaded/EVWELLCOME/event_661/Draft_agenda_for_WT_December_2018.pdf
Join lecture: Nicky Mulder, Han Brunner and Joaquin Dopazo
Presentation carried out by CNAG's director, Ivo Gut, at the course: Identification and analysis of sequence variants in sequencing projects: fundamentals and tools.
IRIDA's Genomic epidemiology application ontology for data standardization, integration and sharing. Presented at IMMEM XI in Estoril, Portugal, March 11 2016.
Open Frame Sequencing™ is a universal tool that allows planning comprehensive genetic diagnostics personalized for each Patient. This solution is dedicated to specialists who expect flexible approach, efficient cooperation and “tailor made” solutions in their daily work.
HGP was conceived in 1984 & officially begun in earnest in October 1990.
HGP is a large multicentric, international collaborative venture, the main aim of which is to determine the nucleotide sequence of the entire human nuclear genome.
In 1997, United States established the National Human Genome Research Institute (NHGRI).
The HGP was an international research groups from six countries- USA, UK, France, Germany, Japan and China, & several laboratories and a large no. of scientists and technicians from various disciplines.
How to transform genomic big data into valuable clinical informationJoaquin Dopazo
How to transform genomic big data into valuable clinical information
The impact of genomics in translational medicine: present view
13th October 2014, Vall d’Hebron Institute of Research (VHIR), Barcelona, Spain
Presentation by Justin Zook at GRC/GIAB ASHG 2017 workshop "Getting the most from the reference assembly and reference materials" on benchmarks for indels and structural variants.
Similar to The Transforming Genetic Medicine Initiative (TGMI) (20)
Presentation at IMGC 2019 workshop describing the latest improvements to the mouse reference genome assembly and analyses performed in preparation for the next release of the mouse genome assembly (GRCm39).
Presentation at 2019 ASHG GRC/GIAB workshop describing history of the human reference genome, current curation efforts and future plans, and the relationship of all 3 to efforts to produce a human pan-genome.
Platform presentation at ASHG 2019 describing recent updates to the human reference genome assembly (GRCh38) and future plans with relevance to pan-genomic representations.
Presentation at 2019 ASHG GRC/GIAB workshop describing goals and progress of the telomere-to-telomere consortium to generate a genome assembly that provides representation of all sequences, including repetitive regions.
Presentation at 2019 ASHG GRC/GIAB workshop describing features and recent updates to the vg toolkit, including examples of comparisons to other methods used for alignment and variant detection.
Presentation at 2019 ASHG GRC/GIAB workshop describing recent updates to the MANE project, which aims to provide matched annotation from RefSeq and GENCODE.
Presentation at PanGenomics in the Cloud Hackathon, run by NCBI at UCSC (https://ncbiinsights.ncbi.nlm.nih.gov/2019/02/06/pangenomics-cloud-hackathon-march-2019/). Presents points to consider about the adoption of a pangenome reference, emphasizing aspects for long-term data management and wide-spread adoption.
Presentation by Benedict Paten at GRC/GIAB ASHG 2017 workshop "Getting the most from the reference assembly and reference materials" on updates to the human reference assembly, GRCh38.
Presentation by Valerie Schneider at GRC/GIAB ASHG 2017 workshop "Getting the most from the reference assembly and reference materials" on updates to the human reference assembly, GRCh38.
Presentation by Tina Graves-Lindsay at GRC/GIAB ASHG 2017 workshop "Getting the most from the reference assembly and reference materials" on production of reference grade assemblies for various human populations.
Presentation by Fritz Sedlazeck at GRC/GIAB ASHG 2017 workshop "Getting the most from the reference assembly and reference materials" on characterizing human structural variation.
Presentation by Karen Miga at GRC/GIAB ASHG 2017 workshop "Getting the most from the reference assembly and reference materials" on centromere assemblies.
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.
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
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
3. Nazneen Rahman
Paul Flicek Caroline Wright
Sian Ellard David Fitzpatrick
Ewan Birney
Fiona Cunningham
Graeme BlackHelen Firth
Gerton Lunter
Matthew Hurles
Patrick Chinnery
TGMI PIs
5. Transforming genetic medicine
Must ensure the wealth of existing medical
genetic knowledge informs our use of current
and future technology, if we are to do more
right and less wrong.
‘The past is never dead, it’s not even past.’ William Faulkner
8. Genetic medicine 1990-2010
GENE ‘MENDELIAN’
DISORDERS
Prior to NGS, genetic medicine was phenotype-driven.
Meticulous phenotyping used to decide which genes to test.
9. Genetic medicine 2020
GENE ‘MENDELIAN’
DISORDERS
With NGS, genetic medicine becomes genotype-driven and
can potentially be large-scale and routine.
10. Genetic medicine 2010-2016
GENE ‘MENDELIAN’
DISORDERS
With NGS, genetic medicine can be genotype-driven. But as
the processes are not well formed phenotyping often used
(often incorrectly) to decide which data is ‘relevant’.
11. TGMI aims to undertake conceptual,
foundational research to deliver
practical solutions to make genetic
medicine work
12. TGMI Aims
1. To provide robust, comprehensive information on
links between genes and human disease in a user-
friendly interface.
2. To develop standardised frameworks for consistent
clinical annotation and reporting of gene variation.
3. To develop approaches to deliver fast, automated,
high-throughput, large-scale variant interpretation.
4. To develop and validate flexible, multipurpose
analytical processes to maximise clinical and research
utilities of genetic testing.
13. GENES
Gene 1
Gene 20,000
For each gene ask qn:
Are germline mutations known to
‘cause’ a human disorder
YES – red (should not become
blue)
NO – blue (some will become
red)
All others – grey (further work
to classify to red or blue)
Gene Disease Map
DISEASES
Many complexities
at phenotype level.
‘Mendelian’
diseases
14. Why this is needed
Q: How many disease genes are there?
A: Depends who and how you ask.
OMIM: ‘genes phenotype-causing mutation’ = 3416
‘phenotype description, molecular basis known’ = 4482
BioMart: Ensembl Genes: + Swiss Prot IDs and OMIM
phenotype = 3268
Gene Cards: ‘disease genes’ = 9578
15. TGMI Aims
1. To provide robust, comprehensive information on
links between genes and human disease in a user-
friendly interface.
2. To develop standardised frameworks for consistent
clinical annotation and reporting of gene variation.
3. To develop approaches to deliver fast, automated,
high-throughput, large-scale variant interpretation.
4. To develop and validate flexible, multipurpose
analytical processes to maximise clinical and research
utilities of genetic testing.
16. TGMI – Aim 2
2.1 – Defining a Clinical Annotation Reference
System (CARS)
2.2 – Defining a Clinical Sequencing Notation
(CSN)
2.3 – Development and distribution of
conversion tools
17. Why this is needed
• In the clinic and research settings there is
huge variability in annotation of genetic
variation at every level (gene name, transcript
choice, variant annotation etc).
• This inevitably compromises data integration,
and clinical utility and fosters errors and
harms.
18. The CARS
• The Clinical Annotation Reference System
(CARS) encompasses the set of protein-coding
genes, the set of reference transcripts and
proteins corresponding to the genes, and a
Clinical Sequencing Notation (CSN) for
annotation of variation according to the
sequences.
• Defined against the reference human
genome.
19. TGMI gene set working criteria
• Has an HGNC ID
• Has an annotated start (which can be non-
methionine)
• Has an annotated stop
• Occurs on chromosomes 1-22, X, Y, or MT
• Has a gene and transcript biotype of “protein-
coding” from Ensembl (release 84)
20. The TGMI gene working set is
comprised of 18,885 genes
21. Clinical reference transcripts
1. Sequences must be based on the reference human
genome.
2. The system must allow flexible iteration without
compromising stability or clarity of sequence selection.
3. Reference transcripts must have durability, i.e. historical
sequences used for clinical reporting that are
subsequently superseded must remain available.
4. The reference transcript set should include as few
sequences as possible (one per gene for most genes) but
as many as required.
5. The reference transcript set must be easily available and
usable to encourage universal uptake.
22. CSN – Clinical Sequencing Notation
• Once transcript is selected, the observed variant
must be named according to its relative difference
from the reference.
• Fixed, standardised, automatic process for
annotation of sequence variation
• Consistent with historical HGVS guidelines
23. TGMI Aims
1. To provide robust, comprehensive information on
links between genes and human disease in a user-
friendly interface.
2. To develop standardised frameworks for consistent
clinical annotation and reporting of gene variation.
3. To develop approaches to deliver fast, automated,
high-throughput, large-scale variant interpretation.
4. To develop and validate flexible, multipurpose
analytical processes to maximise clinical and research
utilities of genetic testing.
24. Traditional interpretation process
1. Leveraging generic predictors, e.g. evolutionary
conservation, protein structural features, impact on
splicing etc to predict the functional consequences
of individual variants (done in lab).
2. Leveraging expert assessment of clinical impact
through disease and gene specific knowledge about
the phenotype, genetic architecture, genotype-
phenotype correlations, personal and family history
and variant segregation etc (done in clinic).
25. Interpretation requirements
1. High-throughput + large volume
2. Fast turnaround
3. Integrated into NGS pipelines
4. Integrated into clinical pipelines
5. Intelligible and usable by non-expert/patients
27. Variant Phenotype
Frequency of phenotype
Mechanism of pathogenicity
Inheritance pattern
Attribution of gene for
phenotype
Penetrance of gene for
phenotype
Population variation
Variability of gene
Gene structure/function
Much useful information can be utilised and automated so
that the required manual curation can be focussed on the
~2-5% of variants where it is required.
28. TGMI Aims
1. To provide robust, comprehensive information on
links between genes and human disease in a user-
friendly interface.
2. To develop standardised frameworks for consistent
clinical annotation and reporting of gene variation.
3. To develop approaches to deliver fast, automated,
high-throughput, large-scale variant interpretation.
4. To develop and validate flexible, multipurpose
analytical processes to maximise clinical and research
utilities of genetic testing.
31. All input is welcome!
• The TGMI is keen to hear from and engage with anyone
interested in our aims. We are grateful for any input into
what is needed in genetic medicine, how those needs are
best met, and whether our solutions work.
• How to stay in touch:
– http://theTGMI.org
– info@theTGMI.org
– Weekly blog
– Twitter: @theTGMI