An Introduction to Biology with Computers
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The document discusses the intersection of biology and computational science, focusing on bioinformatics and computational biology's role in genomics and complex human diseases. It highlights the importance of big data in understanding genetic variations, improving disease prevention and treatment, and utilizing machine learning for predictive modeling. Through various case studies and examples, it emphasizes the application of computational methods to real-world problems, particularly in cancer and neurodegenerative diseases.
![• data analysis method that automates analytical model building
• make data driven predictions or discover patterns without explicit human intervention
• Useful when have complex problems and lots of data (‘big data’)
Machine Learning
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• Our goal isn’t to make perfect guesses, but to make useful guesses—we want to
build a model that is useful for the future](https://image.slidesharecdn.com/bnlnewcenturybioinfclassaug2017ss-170829152844/85/An-Introduction-to-Biology-with-Computers-28-320.jpg)
![Take-Home Message
• Genomics generates big data to address complex biological problems, e.g., improving human disease prevention, diagnosis,
prognosis, and treatment efficacy
• Computers and math are necessary to advance biological research (may be referred to as computational biology,
bioinformatics, systems biology, data science, statistical biology, biostatistics, etc.)
• Machine learning is a data analysis method (and subfield of computer science) that automate analytical model building to
make data driven predictions or discover patterns without explicit human intervention (algorithms are implemented in code)
• Machine learning is useful when we have complex problems with lots of ‘big’ data
• ‘Wet lab’ and ‘dry lab’ biology inform one another—>both are biology!
74
Computer
Data
Program
Output
Traditional Programming
Computer
[2,3]
+
5
Computer
Data
Output
Program
Machine Learning
Computer
[2,3]
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+](https://image.slidesharecdn.com/bnlnewcenturybioinfclassaug2017ss-170829152844/85/An-Introduction-to-Biology-with-Computers-77-320.jpg)
An Introduction to Biology with Computers
- 2. • My background • ‘Genomical’ Data: the Necessity of Biology with Computers • Introduction to Bioinformatics and Computational Biology • Applications of Computational Biology in Genomics
- 3. • My background • ‘Genomical’ Data: the Necessity of Biology with Computers • Introduction to Bioinformatics and Computational Biology • Applications of Computational Biology in Genomics
- 5. Postdoctoral Fellow 5 • HudsonAlpha Institute for Biotechnology, 2014-2017 – Applying machine learning, big data integraiton and genomics to complex human disease to improve disease prevention, detection, treatment, and monitoring – William J. Maier III Fellowship in Cancer Prevention
- 6. 6 PSA: Any Research Experience is Useful When You’re Starting Out • Catfish virus genes increasing disease susceptibility • Using bacteria to clean hydrocarbons from ship bilge water • Hormone effect on kidney mitochondria and obesity • Reverse engineering electromagnetic flow probes • Using bacteria to produce ethanol • Mechanisms of oxidative stress in the brain
- 7. • My background • ‘Genomical’ Data: the Necessity of Biology with Computers • Introduction to Bioinformatics and Computational Biology • Applications of Computational Biology in Genomics
- 8. 8American Cancer Society, 2015 & Harvard NeuroDiscovery Center, 2017. Cancer: • Men have a 1 in 2 lifetime risk of developing cancer and a 1 in 4 lifetime risk of dying from cancer • Women have a 1 in 3 lifetime risk of developing cancer and a 1 in 5 lifetime risk of dying from cancer Psychiatric Illness: • 1 in 4 American adults suffere from a diagnosable mental disorder in any given year • ~6% suffer serious disabilities as a result Neurodegenerative Disease: • ~6.5M Americans suffer (AD, PD, MS, ALS, HD), expected to rise to 12M by 2030 Complex Human Diseases: usually caused by a combination of genetic, environmental and lifetyle factors (most of which have not yet been identified)
- 9. • Which patients are high risk for developing disease? • What are early biomarkers of disease? • Which patients are likely to be short/long term disease survivers? • What therapies might a patient benefit from? 9 Improve disease prevention, diagnosis, prognosis, and treatment efficacy Complex problems
- 10. Genomics • Understanding the function of the genome (total genetic material) and how it relates to human disease (studying all of the genes at once!) • The sequencing of the human genome paved the way for genomic studies • Our goal it identify genetic/genomic variation associated with disease to improve patient care 10
- 11. 11 Sequencing
- 12. 12
- 13. 12
- 14. Image from encodeproject.org 13 Improve disease prevention, diagnosis, prognosis, and treatment efficacy
- 15. Cells, Tissues, & Diseases Functional Annotations Image from encodeproject.org 13 Improve disease prevention, diagnosis, prognosis, and treatment efficacy Multidimensional Data Sets Big Data
- 16. 15 Case study: The Cancer Genome Atlas • Mulitiple data types for 11,000+ patients across 33 tumor types • 549,625 files with 2000+ metadata attributes • >2.5 Petabytes of data 1 Petabyte of Data = 20M four-drawer filing cabinets filled with text or 13.3 years of HD-TV video or ~7 billion Facebook photos or 1 PB of MP3 songs requires ~2,000 years to play
- 19. • My background • ‘Genomical’ Data: the Necessity of Biology with Computers • Introduction to Bioinformatics and Computational Biology • Applications of Computational Biology in Genomics
- 20. Cells, Tissues, & Diseases Functional Annotations mage from encodeproject.org and xorlogics.com. 19 Improve disease prevention, diagnosis, prognosis, and treatment efficacy Multidimensional Data Sets
- 21. Cells, Tissues, & Diseases Functional Annotations mage from encodeproject.org and xorlogics.com. 19 Improve disease prevention, diagnosis, prognosis, and treatment efficacy Multidimensional Data Sets • We have lots of data and complex problems • We want to manage lots of data and make data-driven predictions
- 22. Cells, Tissues, & Diseases Functional Annotations mage from encodeproject.org and xorlogics.com. 20 Multidimensional Data Sets Complex problems + Big Data —> Computer Science + Mathematics
- 23. Computational Biology and Bioinformatics *Disclaimer: My Opinion 21 • Computational biology is the application of computer science and mathematics to problems in biology • Not just genomics! e.g., biophysics, biochemistry, etc. • The terms ‘bioinformatics’ and ‘computational biology’ are often used interchangeably: • Bioinformatics is often associated with the development of software tools, databases, and visualization methods • Computational biology is often used to describe data analysis, algorithm development, and mathematical modeling Other terms you might hear to describe the interdiscipinary field of biology/math/computer science: Data Science, Systems Biology, Statistical Biology, Biostatistics, and Genomics (implicit)
- 24. 22 Wet Lab
- 25. 23 Generally computational skills are: • In demand • Flexible • Highly transferable Computational people can work from anywhere… but that also means they can work from anywhere
- 27. Cells, Tissues, & Diseases Functional Annotations mage from encodeproject.org and xorlogics.com. 25 Multidimensional Data Sets Complex problems + Big Data —> Machine Learning!
- 28. • data analysis method that automates analytical model building • make data driven predictions or discover patterns without explicit human intervention • Useful when have complex problems and lots of data (‘big data’) Machine Learning 26 Computer Data Program Output Traditional Programming Computer [2,3] + 5 Computer Data Output Program Machine Learning Computer [2,3] 5 + • Our goal isn’t to make perfect guesses, but to make useful guesses—we want to build a model that is useful for the future
- 32. Fisher’s/Anderson's iris data set: measurements (cm) of the sepal length and width and petal length and width (4 features) for 50 flowers from each of 3 species (Iris setosa, versicolor, and virginica) Iris Dataset in R 29
- 36. Iris Data: Adding Regularization (LASSO) •Model building with a large # of features for a moderate number of samples can result in ‘overfitting’ —the model is too specific to the training set and not generalizable enough for accurate predictions with new data •Regularization is a technique for preventing this by introducing tuning parameters that penalize the coefficients of variables that are linearly dependent (redundant) •This results in FEATURE SELECTION •Ridge regression and LASSO regression are methods of regression with regularization 33 Computer Petal.Length Sepal.Width Sepal.Length Petal.Width Petal.Width~ 0.968*Sepal.Length + 0.187 Petal.Width ~ A*Petal.Length + B*Sepal.Width + C* Sepal.Length + b 0 0 Petal.Width ~ 0*Petal.Length + 0*Sepal.Width + C* Sepal.Length + b Petal.Width ~ Sepal.Length + b p value < 2.2*10-16
- 37. Iris Data: Decision Trees • Decision trees can take different data types (categorical, binary, numeric) as input/output variables, handle missing data and outliers well, and are intuitive • Decision tree limitations include that each decision boundary at each split is a concrete binary decision and the decision criteria only consider one input feature at a time (not a combination of multiple input features) • Examples: Video games, clinical decision models 34 Petal.Length < 2.35 cm Setosa (40/0/0) Petal.Width < 1.65 cm Versicolor (0/40/12) Virginica (0/0/28)
- 38. Other Machine Learning Methods • Ensemble Methods (combine models, e.g. bagging and boosting) • Neural Nets (inspired by the human brain) • Naive Bayes (based on prior probabilities) • Hidden Markov Models (Bayesian network with hidden states) • K Nearest Neighbors (instance-based learning —clustering!) • Support Vector Machines (discriminator defined by a separating hyperplane) • Additional Ensemble Method Approaches (combining multiple models) • And new methods coming out all the time… 35
- 39. Other Machine Learning Methods • Ensemble Methods (combine models, e.g. bagging and boosting) • Neural Nets (inspired by the human brain) • Naive Bayes (based on prior probabilities) • Hidden Markov Models (Bayesian network with hidden states) • K Nearest Neighbors (instance-based learning —clustering!) • Support Vector Machines (discriminator defined by a separating hyperplane) • Additional Ensemble Method Approaches (combining multiple models) • And new methods coming out all the time… Raw Data Clean/Normalize Data Training Set Test Set Build Model Test Apply to New Data (Validation Cohort or Model Application) Tune Model 35 Algorithm Selection is an Important Step!
- 40. • My background • ‘Genomical’ Data: the Necessity of Biology with Computers • Introduction to Bioinformatics and Computational Biology • Applications of Computational Biology in Genomics
- 41. 37 Example Computational Biology Experiments and Tasks: • Example 1: Identify Variants Associated with a Predisposition to ALS • Annotation • Databasing • Statistical Programming (analysis + visualization) • Hypothesis-Generating Research • Example 2: Develop Biomarkers for Kidney Cancer Diagnosis • Statistical Programming (analysis + visualization) • Machine Learning • Direct Clinical Application • Interdependent and Complementary ‘Wet’/‘Dry’ Biology Research • Example 3: Generate Pan-Cancer Models of Patient Prognosis • Statistical Programming (analysis + visualization) • Machine Learning • Software Development • Computational Research
- 42. 38 Example Computational Biology Experiments and Tasks: • Example 1: Identify Variants Associated with a Predisposition to ALS • Annotation • Databasing • Statistical Programming (analysis + visualization) • Hypothesis-Generating Research • Example 2: Develop Biomarkers for Kidney Cancer Diagnosis • Statistical Programming (analysis + visualization) • Machine Learning • Direct Clinical Application • Interdependent and Complementary ‘Wet’/‘Dry’ Biology Research • Example 3: Generate Pan-Cancer Models of Patient Prognosis • Statistical Programming (analysis + visualization) • Machine Learning • Software Development • Computational Research
- 43. Amyotrophic Lateral Sclerosis (ALS) • Also known as Lou Gehrig’s disease • Progressive neurodegenerative disease causing muscle weakness and atrophy due to degeneration of motor neurons • ~5,600 new cases in the US annually • Median survival time from onset to death is 39 months Photo: phillysportshistory.com 39
- 44. 40 ALS Symptoms, Diagnosis, and Treatment • Ini$al symptoms and progression rates vary • No single test or procedure for defini$ve diagnosis • Riliuzole improves survival by months and physical therapy can help delay loss of strength and maintain endurance • Breathing support when the muscles that assist breathing weaken alsa.org
- 49. 44 Iden%fying Variants with Exome Sequencing Compare Variants CTACGATCGA Control Group (n=~6500) CTAGGATCGA Affected Pa%ent Group (n=~3000) • Exome Sequencing: Iden%fy varia%on in coding regions (genes) • Advantage: Interpretability and lower cost compared to whole genome sequencing Intergenic Gene Exon Intron
- 50. 45 Gene Burden Tes+ng of Rare Variants Compare Frequency Distribu+ons • Significant enrichment of qualifying variants between groups Count Qualifying Variants: • Count qualifying variants in a gene-based collapsing analysis including exons mee=ng coverage benchmarks Example: Loss of Func=on (splice, nonsense, or frameshiE) Gene X: Variant Enrichment Controls Cases • SOD1: First gene associated with familial ALS (enzyme that destroys free superoxide radicals) ✔
- 51. 46 Iden%fying Novel ALS Genes: TBK1 Cirulli & Lasseigne, et al. 2015. (under review). Wild, et al. 2011. Gleason, et al. 2011. Pilli, et al. 2012. Kachaner, et al. 2012. Komatsu, et al. 2012. RVIS • Non-benign variants: 1.097% of cases • LoF variants: 0.382% of cases LOF variant Case/control variant Missense variant Splice variant Case variant Control variant • TBK1 interacts with other ALS-associated genes that play important roles in autophagy and inflammaWon Amyotrophic lateral sclerosis aggregates Cirulli & Lasseigne, et al. 2016. Wild, et al. 2011. Gleason, et al. 2011. Pilli, et al. 2012. Kachaner, et al. 2012. Komatsu, et al. 2012.
- 52. 47 Identifying Novel ALS Genes: NEK1 • NEK1: multi-functional kinase, role in cilia formation and centrosome function, never previously linked to ALS • Follow-up custom capture sequencing (1,318 additional cases and 2,371 additional controls) further supports NEK1’s role in ALS predisposition QQ plot: Dominant LoF model 0 1 2 3 4 Expected –log10(p) 0 2 4 6 Observed –log10(p) Cirulli & Lasseigne, et al. 2015. (under review) Cirulli & Lasseigne, et al. 2015.
- 53. 48 NEK1 associates with ALS2 and VAPB • To investigate binding partners, we performed an unbiased screen of NEK1-interacting proteins in human kidney epithelial cells via AP-MS • Interactions validated by immunoprecipitation followed by western blotting of co-expressed proteins in neuronal NSC-34 cells • Suggests NEK1 may contribute to ALS through multiple mechanisms: – ALS2 and VAPB control cytoplasmic trafficking of endosomes and lipids in diverse cell lineages, respectively, both biological functions that are now appreciated as important in other neurodegenerative diseases Cirulli & Lasseigne, et al. 2015. (under review) Recessive causes of ALS when mutated: ALS2: RAB guanine nucleotide exchange factor VAPB/VAPA: transmembrane proteins that transfer lipids from the ER to the plasma membrane Cirulli & Lasseigne, et al. 2015.
- 54. 49 Example Computational Biology Experiments and Tasks: • Example 1: Identify Variants Associated with a Predisposition to ALS • Annotation • Databasing • Statistical Programming (analysis + visualization) • Hypothesis-Generating Research • Example 2: Develop Biomarkers for Kidney Cancer Diagnosis • Statistical Programming (analysis + visualization) • Machine Learning • Direct Clinical Application • Interdependent and Complementary ‘Wet’/‘Dry’ Biology Research • Example 3: Generate Pan-Cancer Models of Patient Prognosis • Statistical Programming (analysis + visualization) • Machine Learning • Software Development • Computational Research
- 55. 50 Example Computational Biology Experiments and Tasks: • Example 1: Identify Variants Associated with a Predisposition to ALS • Annotation • Databasing • Statistical Programming (analysis + visualization) • Hypothesis-Generating Research • Example 2: Develop Biomarkers for Kidney Cancer Diagnosis • Statistical Programming (analysis + visualization) • Machine Learning • Direct Clinical Application • Interdependent and Complementary ‘Wet’/‘Dry’ Biology Research • Example 3: Generate Pan-Cancer Models of Patient Prognosis • Statistical Programming (analysis + visualization) • Machine Learning • Software Development • Computational Research
- 57. Kidney Cancer Diagnosis and Treatment • ~65,000 new cases in the United States each year (10th most common cancer) • If caught early, patients typically do well • Treatment for advanced cases has improved in recent years, but the best drugs only increase disease free progression after resection by months and have harsh side effects • Considered non-responsive to traditional radiation and chemotherapies 52 81% Survival at 5 years
- 58. Kidney Cancer Diagnosis and Treatment • ~65,000 new cases in the United States each year (10th most common cancer) • If caught early, patients typically do well • Treatment for advanced cases has improved in recent years, but the best drugs only increase disease free progression after resection by months and have harsh side effects • Considered non-responsive to traditional radiation and chemotherapies 52 74% Survival at 5 years
- 59. Kidney Cancer Diagnosis and Treatment • ~65,000 new cases in the United States each year (10th most common cancer) • If caught early, patients typically do well • Treatment for advanced cases has improved in recent years, but the best drugs only increase disease free progression after resection by months and have harsh side effects • Considered non-responsive to traditional radiation and chemotherapies 52 53% Survival at 5 years
- 60. Kidney Cancer Diagnosis and Treatment • ~65,000 new cases in the United States each year (10th most common cancer) • If caught early, patients typically do well • Treatment for advanced cases has improved in recent years, but the best drugs only increase disease free progression after resection by months and have harsh side effects • Considered non-responsive to traditional radiation and chemotherapies 52 8% Survival at 5 years
- 62. DNA Methylation at CpGs: The “Fifth” Base 54 Cytosine 5-Methyl Cytosine Regulates biological processes without altering genetic blueprint (DNA sequence) DNA Methylation Functions: • DNA-protein interactions • Cellular differentiation • Transposable element suppression • X-inactivation • Genomic imprinting • Gene regulation • DNA methylation as early diagnostic biomarkers: • Early events in carcinogenesis • Stable DNA mark and can be quantitatively measured
- 65. From Bench To Bedside: ’liquid biopsies’ from peripheral fluids Cell-free DNA Blood Test Urine Test Patient with Kidney cancer •Early diagnosis for non-specific symptoms •Clarify between small benign lesions and malignant tumors •Follow patients after surgery or during treatment to watch for recurrence •Monitor molecular changes associated with patient outcome
- 66. 58 Example Computational Biology Experiments and Tasks: • Example 1: Identify Variants Associated with a Predisposition to ALS • Annotation • Databasing • Statistical Programming (analysis + visualization) • Hypothesis-Generating Research • Example 2: Develop Biomarkers for Kidney Cancer Diagnosis • Statistical Programming (analysis + visualization) • Machine Learning • Direct Clinical Application • Interdependent and Complementary ‘Wet’/‘Dry’ Biology Research • Example 3: Generate Pan-Cancer Models of Patient Prognosis • Statistical Programming (analysis + visualization) • Machine Learning • Software Development • Computational Research
- 67. 59 Example Computational Biology Experiments and Tasks: • Example 1: Identify Variants Associated with a Predisposition to ALS • Annotation • Databasing • Statistical Programming (analysis + visualization) • Hypothesis-Generating Research • Example 2: Develop Biomarkers for Kidney Cancer Diagnosis • Statistical Programming (analysis + visualization) • Machine Learning • Direct Clinical Application • Interdependent and Complementary ‘Wet’/‘Dry’ Biology Research • Example 3: Generate Pan-Cancer Models of Patient Prognosis • Statistical Programming (analysis + visualization) • Machine Learning • Software Development • Computational Research
- 71. Abbreviation Cancer n ACC Adrenocortical Carcinoma 79 BLCA Bladder Urothelial Carcinoma 385 BRCA Breast Invasive Carcinoma 1038 CESC Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma 393 ESCA Esophageal Carcinoma 163 GBM Glioblastoma Multiforme 144 HNSC Head and Neck Squamous Cell Carcinoma 508 KIRC Kidney Renal Clear Cell Carcinoma 525 KIRP Kidney Renal Papillary Cell Carcinoma 266 LAML Acute Myeloid Leukemia 148 LGG Brain Lower Grade Glioma 463 LIHC Liver Hepatocellular Carcinoma 355 LUAD Lung Adenocarcinoma 493 LUSC Lung Squamous Cell Carcinoma 479 MESO Mesothelioma 72 OV Ovarian Serous Cystadenocarcinoma 252 PAAD Pancreatic Adenocarcinoma 167 SARC Sarcoma 248 STAD Stomach Adenocarcinoma 403 Total: 19 Cancers, 6581 Patients The TCGA Dataset 65
- 72. Scaled -log10 Cox p-value -1 2 30 1 ‘Common Survival Genes’ across 19 cancers • ‘Common Survival Genes’ Cox regression uncorrected p-value <0.05 for a gene in at least 9/19 cancers: • 84 genes, enriched for proliferation-related processes including mitosis, cell and nuclear division, and spindle formation • Clustering by Cox regression p- values: 7 ‘Proliferative Informative Cancers’ and 12 ‘Non-Proliferative Informative Cancers’ 68 ESCA STAD OV LUSC GBM LAML LIHC SARC BLCA CESC HNSC BRCA ACC MESO KIRP LUAD PAAD LGG KIRC TopCrossCancerSurvivalGenes * C Ramaker & Lasseigne, et al. 2017.
- 73. Scaled -log10 Cox p-value -1 2 30 1 ‘Common Survival Genes’ across 19 cancers Proliferative Informative Cancers (PICs) 70 ESCA STAD OV LUSC GBM LAML LIHC SARC BLCA CESC HNSC BRCA ACC MESO KIRP LUAD PAAD LGG KIRC TopCrossCancerSurvivalGenes * C Non-Proliferative Informative Cancers (Non-PICs) • ‘Common Survival Genes’ Cox regression uncorrected p-value <0.05 for a gene in at least 9/19 cancers: • 84 genes, enriched for proliferation-related processes including mitosis, cell and nuclear division, and spindle formation • Clustering by Cox regression p- values: 7 ‘Proliferative Informative Cancers’ and 12 ‘Non-Proliferative Informative Cancers’ Ramaker & Lasseigne, et al. 2017.
- 74. 71 Cross-Cancer Patient Outcome Model Cox regression with LASSO feature selection ~20,000 gene expression values Cancer Patient Survival Survival~ -0.104 + 0.086*ADAM12 + 0.037*CKS1 - 0.088*CRYL1 + 0.056*DNA2 + 0.013*DONSON + 0.098*HJURP - 0.022*NDRG2 + 0.031*RAD54B + 0.040*SHOX2 - 0.155*SUOX Ramaker & Lasseigne, et al. 2017. Utility: • Predict patient prognosis • Potentially inform on treatments • Use of metagenes to infer molecular profiles from gene expression data
- 75. Analysis Packages: e.g. ‘ProliferativeIndex’ 72 Ramaker & Lasseigne, et al. Oncotarget, 2017. • Analytical R package available on CRAN and GitHub (continuous integration with Travis CI) • Documented functions and a vignette with examples • Provides users with R functions for calculating and analyzing the proliferative index (PI) from an RNA- seq dataset
- 76. 73 Example Computational Biology Experiments and Tasks: • Example 1: Identify Variants Associated with a Predisposition to ALS • Annotation • Databasing • Statistical Programming (analysis + visualization) • Hypothesis-Generating Research • Example 2: Develop Biomarkers for Kidney Cancer Diagnosis • Statistical Programming (analysis + visualization) • Machine Learning • Direct Clinical Application • Interdependent and Complementary ‘Wet’/‘Dry’ Biology Research • Example 3: Generate Pan-Cancer Models of Patient Prognosis • Statistical Programming (analysis + visualization) • Machine Learning • Software Development • Computational Research
- 77. Take-Home Message • Genomics generates big data to address complex biological problems, e.g., improving human disease prevention, diagnosis, prognosis, and treatment efficacy • Computers and math are necessary to advance biological research (may be referred to as computational biology, bioinformatics, systems biology, data science, statistical biology, biostatistics, etc.) • Machine learning is a data analysis method (and subfield of computer science) that automate analytical model building to make data driven predictions or discover patterns without explicit human intervention (algorithms are implemented in code) • Machine learning is useful when we have complex problems with lots of ‘big’ data • ‘Wet lab’ and ‘dry lab’ biology inform one another—>both are biology! 74 Computer Data Program Output Traditional Programming Computer [2,3] + 5 Computer Data Output Program Machine Learning Computer [2,3] 5 +
- 78. Genomics Requires Team and Individual Expertise in Many Disciplines Because We Are Addressing Complicated Questions 75 Molecular Biology/ Genetics Engineering Computational Biology Computational Infrastructure (IT) Programming yi = βo + β1x1i + β2x2i + β3x3i Mathematics etc…. Communication GENOMICS
- 79. HudsonAlpha: hudsonalpha.org coursera.org and datacamp.com Books: • The Emperor of All Maladies by Siddhartha Mukherjee (History of cancer) • The Gene by Siddhartha Mukherjee (History of genetics) • Genome by Matt Ridley (Human genome) • Headstrong: 52 Women Who Changed Science-and the World by Rachel Swaby (Female scientist profiles) • Rosalind Franklin: The Dark Lady of DNA by Brenda Maddox (Female scientist biography)