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.
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.
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 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 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 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.
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.
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 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 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 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.
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 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 recent updates to the MANE project, which aims to provide matched annotation from RefSeq and GENCODE.
GRC Workshop at Churchill College on Sep 21, 2014. This is Michael Schatz's talk on the theory and practice of representing population data in graph structures.
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 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.
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 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 recent updates to the MANE project, which aims to provide matched annotation from RefSeq and GENCODE.
GRC Workshop at Churchill College on Sep 21, 2014. This is Michael Schatz's talk on the theory and practice of representing population data in graph structures.
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 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.
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 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 Karen Miga at GRC/GIAB ASHG 2017 workshop "Getting the most from the reference assembly and reference materials" on centromere assemblies.
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.
Follow us on: Pinterest
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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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 Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
1. Genome in a Bottle:
Developing benchmark sets for large indels and
structural variants
Justin Zook, Marc Salit, and the GIAB Consortium
NIST Genome-Scale Measurements Group
Joint Initiative for Metrology in Biology (JIMB)
Oct 16, 2017
2. Take-home Messages
• Genome in a Bottle is authoritatively characterizing human
genomes
• Current characterization enables benchmarking of “easier”
variants/regions in germline genomes
– Clinical validation
– Technology development, optimization, and demonstration
• Now working on difficult variants and regions
– Draft variant calls >=20bp available and feedback requested
– Many challenges remain and collaborations welcome!
3. Why are we doing this?
• Technologies evolving rapidly
• Different sequencing and
bioinformatics methods give
different results
• Now have concordance in easy
regions, but not in difficult
regions
• Challenge:
– How do we characterize 6 billion
bases in the genome with high
confidence?
O’Rawe et al, Genome Medicine, 2013
https://doi.org/10.1186/gm432
4. GIAB is evolving
2012
• No human
benchmark
calls available
• GIAB
Consortium
formed
2014
• Small variant
genotypes
for ~77% of
pilot genome
NA12878
2015
• NIST releases
first human
genome
Reference
Material
2016
• 4 new
genomes
• Small
variants for
90% of 5
genomes for
GRCh37/38
2017+
• Characteriz-
ing difficult
variants
5. Genome in a Bottle Consortium
Authoritative Characterization of Human Genomes
Sample
gDNA isolation
Library Prep
Sequencing
Alignment/Mapping
Variant Calling
Confidence Estimates
Downstream Analysis
• gDNA reference materials to
evaluate performance
• GIAB is developing:
– reference materials
– Reference data
– Methods
– Tools to calculate performance
metrics
genericmeasurementprocess
www.slideshare.net/genomeinabottle
6. Bringing Principles of Metrology
to the Genome
• Reference materials
– DNA in a tube from NIST
• Extensive state-of-the-art
characterization
• “Upgradable” as technology
develops
• Commercial innovation
– PGP genomes suitable for
commercial derived products
• Benchmarking tools and software
– with GA4GH
• Enhance new technologies
7. GIAB has characterized 5 human genome RMs
• Pilot genome
– NA12878
• PGP Human Genomes
– Ashkenazi Jewish son
– Ashkenazi Jewish trio
– Chinese son
• Parents also characterized
National I nstituteof S tandards & Technology
Report of I nvestigation
Reference Material 8391
Human DNA for Whole-Genome Variant Assessment
(Son of Eastern European Ashkenazim Jewish Ancestry)
This Reference Material (RM) is intended for validation, optimization, and process evaluation purposes. It consists
of a male whole human genome sample of Eastern European Ashkenazim Jewish ancestry, and it can be used to assess
performance of variant calling from genome sequencing. A unit of RM 8391 consists of a vial containing human
genomic DNA extracted from a single large growth of human lymphoblastoid cell line GM24385 from the Coriell
Institute for Medical Research (Camden, NJ). The vial contains approximately 10 µg of genomic DNA, with the peak
of the nominal length distribution longer than 48.5 kb, as referenced by Lambda DNA, and the DNA is in TE buffer
(10 mM TRIS, 1 mM EDTA, pH 8.0).
This material is intended for assessing performance of human genome sequencing variant calling by obtaining
estimates of true positives, false positives, true negatives, and false negatives. Sequencing applications could include
whole genome sequencing, whole exome sequencing, and more targeted sequencing such as gene panels. This
genomic DNA is intended to be analyzed in the same way as any other sample a lab would process and analyze
extracted DNA. Because the RM is extracted DNA, it is not useful for assessing pre-analytical steps such as DNA
extraction, but it does challenge sequencing library preparation, sequencing machines, and the bioinformatics steps of
mapping, alignment, and variant calling. This RM is not intended to assess subsequent bioinformatics steps such as
functional or clinical interpretation.
Information Values: Information values are provided for single nucleotide polymorphisms (SNPs), small insertions
and deletions (indels), and homozygous reference genotypes for approximately 88 % of the genome, using methods
similar to described in reference 1. An information value is considered to be a value that will be of interest and use to
the RM user, but insufficient information is available to assess the uncertainty associated with the value. We describe
and disseminate our best, most confident, estimate of the genotypes using the data and methods currently available.
These data and genomic characterizations will be maintained over time as new data accrue and measurement and
informatics methods become available. The information values are given as a variant call file (vcf) that contains the
high-confidence SNPs and small indels, as well as a tab-delimited “bed” file that describes the regions that are called
high-confidence. Information values cannot be used to establish metrological traceability. The files referenced in this
report are available at the Genome in a Bottle ftp site hosted by the National Center for Biotechnology Information
(NCBI). The Genome in a Bottle ftp site for the high-confidence vcf and high confidence regions is:
8. Integration of diverse data types and analyses
• Data publicly available
– Deep short reads
– Linked reads
– Long reads
– Optical/nanopore mapping
• Analyses
– Small variant calling
– SV calling
– Local and global assembly
Discover &
Refine
sequence-
resolved calls
from multiple
datasets &
analyses Compare
variant and
genotype calls
from different
methods
Evaluate/
genotype calls
with other
data
Identify
features
associated
with reliability
of calls from
each method
Form
benchmark
calls using
heuristics &
machine
learning
Compare
benchmarks
to high-
quality
callsets and
examine
differences
10. Evolution of high-confidence small variants
Calls
HC
Regions HC Calls
HC
indels
Concordant
with PG
NIST-
only in
beds
PG-only
in beds PG-only
Variants
Phased
v2.19 2.22 Gb 3153247 352937 3030703 87 404 1018795 0.3%
v3.2.2 2.53 Gb 3512990 335594 3391783 57 52 657715 3.9%
v3.3 2.57 Gb 3566076 358753 3441361 40 60 608137 8.8%
v3.3.2 2.58 Gb 3691156 487841 3529641 47 61 469202 99.6%
5-7
errors
in NIST
1-7
errors
in NIST
~2 FPs and ~2 FNs per million NIST variants in PG and NIST bed files
11. Global Alliance for Genomics and Health Benchmarking Task
Team
• Developed standardized
definitions for performance
metrics like TP, FP, and FN.
• Developing sophisticated
benchmarking tools
• Integrated into a single framework
with standardized inputs and
outputs
• Standardized bed files with
difficult genome contexts for
stratification
https://github.com/ga4gh/benchmarking-tools
Variant types can change when decomposing
or recomposing variants:
Complex variant:
chr1 201586350 CTCTCTCTCT CA
DEL + SNP:
chr1 201586350 CTCTCTCTCT C
chr1 201586359 T A
Credit: Peter Krusche, Illumina
GA4GH Benchmarking Team
13. What are we accessing and what is still
challenging?
Type of variant Genome
context
Fraction
of variants
called*
Number of
variants
missing*
How to improve?
Simple SNPs Not repetitive ~97% >100k Machine learning
Simple indels Not repetitive ~93% >10k Machine learning
All variants Low
mappability
<30% >170k Use linked reads and long
reads
All variants Regions not in
GRCh37/38
0 >>100k??? De novo assembly; long reads
Small indels Tandem repeats
and
homopolymers
<50% >200k STR/homopolymer callers; long
reads; better handle complex
and compound variants
Indels 15-50bp All <25% >30k Assembly-based callers;
integrate larger variants
differently; long reads
Indels >50bp All <1% >20k
* Approximate values based on fraction of variants in GATKHC or FermiKit that are
inside v3.3.2 High-confidence regions
14. How can we extend our approach to structural
variants?
Similarities to small variants
• Collect callsets from multiple
technologies
• Compare callsets to find calls
supported by multiple technologies
Differences from small variants
• Callsets have limited sensitivity
• Variants are often imprecisely
characterized
– breakpoints, size, type, etc.
• Representation of variants is poorly
standardized, especially when complex
• Comparison tools in infancy
15. Our strategy
Collect many candidate calls for AJ Trio
• Gather candidate calls from a variety of
approaches
– Many technologies
• Short, linked, and long reads
• Optical and nanopore mapping
– Many approaches
• Small variant callers
• Structural variant callers
• Local and global de novo assemblies
• Community submitted >1 million calls
from 30+ methods using 5+ technologies
Refine/evaluate/genotype candidates
• Obtain sequence-resolved calls as
often as possible using assembly-based
approaches
• Compare sequence predictions of
candidate calls and merge similar calls
• Determine raw data’s support of each
sequence-resolved call and its
genotype
16. Evaluation/genotyping suite of methods
Current approaches
• svviz – maps reads to REF or ALT alleles
– PacBio
– Illumina paired end and mate-pair
– 10X haplotype-separated
• BioNano – compare size predictions
• Nabsys – evaluates large deletions
Future approaches
• Separate haplotypes on other data
types for svviz using whatshap
• Online manual curation of svviz, IGV,
dotplots, gEVAL, etc.
– Volunteers needed!
• PCR-Sanger targeted sequencing
– Collaborations welcome!
17. Integrating Sequence-resolved Calls >=20bp
>1 million calls from 30+ sequence-resolved callsets from 4 techs for
AJ Trio
>500k unique sequence-resolved calls
30k INS and 32k DEL with 2+ techs or 5+
callers predicting sequences <20%
different or BioNano/Nabsys support
28k INS and 29k DEL
genotyped by svviz in 1+
individuals
v0.4.0
18. Size Distribution of v0.4.0 Calls
Not Tandem Repeat
Tandem Repeat
Deletions Insertions
Alu
LINE
Alu
LINE
20. Insertion sequence prediction accuracy differs
between methods
Relative Distance from exact match
Illumina local
assembly
PacBio raw
read
PacBio consensus
assembly
22. Outstanding challenges and future work
• Large sequence-resolved insertions
• Many fewer multi-kb insertions
than multi-kb deletions
• Dense calls
• ~1/3 v0.4.0 calls are within 1kb of
another v0.4.0 call
• Sequence-resolved insertion size
doesn’t always match BioNano
• Phasing will be important for
these (e.g., with 10X, whatshap)
• Calls with inaccurate or incomplete
sequence change
• Exploring training a model to
predict sequence accuracy
• Homozygous Reference calls
• Can we definitively state there is
no SV in some regions?
• E.g., using diploid assembly?
• Benchmarking tool development
• How to compare SVs to a
benchmark?
• What performance metrics are
important?
23. New public data planned for late 2017
• PacBio Sequel sequencing of
GIAB Chinese trio
– Collaboration with Mt. Sinai
– 60x/30x/30x coverage planned
– Potentially >15kb N50 read length
• Oxford Nanopore sequencing of
Ashkenazim trio
– Collaboration with Nick Loman and
Matt Loose
– ~50x/25x/25x coverage planned
– Ultralong read sequencing (50-
100kb+ N50 read length)
24. New Samples
Additional ancestries
• Shorter term
– Use existing PGP individual samples
– Use existing integration pipeline
• Data-based selection
– Proportion of potential genomes from
different ancestries
• 3 to 8 new samples
• Longer term
– Recruit large family
– Recruit trios from other ancestry groups
Cancer samples
• Longer term
• Make PGP-consented tumor and
normal cell lines from same individual
• Select tumor with diversity of mutation
types
25. Take-home Messages
• Genome in a Bottle is authoritatively characterizing human
genomes
• Current characterization enables robust benchmarking of “easier”
variants/regions
• Actively working on difficult variants and regions
– Draft variant calls >=20bp available – feedback requested!
• New public long and ultralong read datasets coming!
• What can we help enable?
– Clinical applications – precision medicine
– Research applications – how to know new methods are measuring difficult
regions/variants well
26. Acknowledgements
• NIST/JIMB
– Marc Salit
– Jenny McDaniel
– Lindsay Vang
– David Catoe
– Lesley Chapman
• Genome in a Bottle Consortium
• GA4GH Benchmarking Team
• FDA
27. For More Information
www.genomeinabottle.org - sign up for general GIAB and Analysis Team google group emails
github.com/genome-in-a-bottle – Guide to GIAB data & ftp
www.slideshare.net/genomeinabottle
Data: http://www.nature.com/articles/sdata201625
Global Alliance Benchmarking Team
– https://github.com/ga4gh/benchmarking-tools
– precision.fda.gov – GA4GH benchmarking app
Biweekly Analysis Team calls (open to all)
– https://groups.google.com/forum/#!forum/giab-analysis-team
Public workshops
– Next workshop Jan 25-26, 2018 in Stanford, CA
– http://jimb.stanford.edu/giabworkshops for info and registration
NIST/JIMB postdoc opportunities available!
Justin Zook: jzook@nist.gov
Marc Salit: salit@nist.gov