Dylan Lawless

Postdoctoral researcher, Switzerland

About Me

  • Postdoc scientist.
  • Human genomics & immunology.
  • Large-scale bioinformatics and wet-lab, molecular genetics, immunology.
  • WGS, exome, SNV, CNV, rare disease, RNAseq, somatic mutation, pipeline dev, statistics.
  • Current projects in host-pathogen genomic interactions to viruses, bacterial sepsis, and genetic susceptibility to immune disorders.
  • Data types include whole genome sequencing, GWAS, pathogen sequencing, methylation, RNA, an array of other clinical data.
  • I specialise in the genetics of the primary immune system and response to infection.
  • Working with a wide range of specialists from international teams. Collaborative research projects in human health with a lasting impact based on open, reproducible science.

Current position

Fellay Lab – Human Genomics of Infection and Immunity, EPFL, Switzerland

https://people.epfl.ch/dylan.lawless

Scientist

2018 – Present

Applying next generation technolgies to translate research into practice.

Global Health Institute, School of Life Sciences, EPFL. Fields of expertise include Bioinformatics, Innate and adaptive immunology, Primary immunodeficiencies, Autoinflammatory disease, NGS experiments and analysis, Functional and computational immunology, Privacy in personal health.

Education

University of Leeds

medicinehealth.leeds.ac.uk/medicine

PhD Genomics Immunology

2015 - 2018

Novel genetic discoveries in rare primary immunodeficiencies.

Trinity College Dublin

tcd.ie/Biochemistry

MSc Immunology (Distinction)

2013 - 2014

Exploring the therapeutic potential of a peptide derived from a poxviral immune evasion protein.

University College Cork

www.ucc.ie/en/microbiology

BSc Microbiology (Honours)

2009 - 2013

Majors in medical microbiology, virology, and research on Innate immunity in microbiology.

Experience

EPFL Postdoctoral study

epfl.ch/labs/fellay-lab

2018-current

Human immunology and translational genomics. Working on large-scale human genomics, genetics of immune disorders, host-pathogen genetics, and genomic privacy in personal health. Collaborating on several national and international initiatives in human genetics and health. Skilled in big data analyses, state of the art methods in genomic analysis, statistics, study design, student supervision, team coordination, international project management, presentation, and scientific writing.

University of Leeds PhD

medicinehealth.leeds.ac.uk/medicine

2015 - 2018

PhD in Genomics and Immunology in novel genetic discoveries in rare primary immunodeficiencies. Genetic discoveries in immunology, combing wet-lab and bioinformatics. Merging clinical research with translational medicine. Using next-generation sequencing for patients with rare severe genetic disorders, to identify genetic determinants of disease. Studying in vivo and in vitro mechanisms to apply novel findings to human health. Experienced in whole genome and exome sequencing, molecular genetics, protein expression, a wide range of functional assays, big data analyses, statistical analysis, producing novel computational analysis, and applying best practices in state of the art bioinformatics.

Trinity College Dublin MSc

tcd.ie/Biochemistry

2013 - 2014

Exploring the therapeutic potential of a peptide derived from a poxviral immune evasion protein. Studying a wide range of applications in immunology, human pathogens, allergy, immunodeficiency. Carried out functional immunology work exploring the therapeutic potential of peptides derived from viral immune evasion proteins. Skilled in protein expression, immunological assays, virology, protein structure work.

ACM global

2014 – 2015

Analytical Scientist. Performing a wide range of esoteric assays for a number of clinical trials in human health. Handling a range of human tissues including whole blood preparation, flow cytometry, ELISA. Managing deadlines, data entry, GLM skills, and shared projects.

Awards

2019

The European Society of Human Genetics best poster candidate.

2018

Microsoft Azure Research Award. Data Science and Machine Learning in Predictive Genomics.

2017

Wellcome Genome Campus, Cambridge Travel Grant.

2015

University of Leeds 110 Anniversary Postgraduate Research Scholarship.

2014

TCD 1st place Postgraduate Poster prize.

Scientific skills and other

Independent research

State of the art methods in genomic analysis, statistics, study design, team coordination, project management, presentation, scientific writing, deductive reasoning, critical thinking, and multidisciplinary flexibility. Leading a number of international research projects. Project supervision of 5 MSc thesis and PhD, and teaching on numerous courses.

Bioinformatics

Responsible for human bioinformatic experiments and pipelines in PhD lab 2015-2019 and in PostDoc lab 2018-current.

  • Variant priorisation and variant effect prediction
  • WGS, exome, SNV, CNV, RNAseq, Germline, Somatic mutation, Cancer, Tumor
  • Handling genetic data formats FASTQ, BAM, CRAM, SAM, gVCF, ASN.1, json, plink, etc.
  • GATK best practices, Popular genomic database and reference panels, Popular variant prediction algorithm/databases, Annotation of variants with custom databases, VEP, dbNSFP, ANNOVAR, etc
  • ACMG standards and guidelines for interpretation of variants, Nomenclature standards incl. HGVS, HGNC
  • Large-scale NGS initiatives, National and international, Privacy in personal health, Big data analyses, Population genomics, Pedigree analysis, Clinical genetics.
  • Pathogen genetics, Viral, Bacterial, Phylogenetics and epidemiology.

Statistics

Association testing, Mixed models, Inference, Variance, Correlation, Regression, Repeated data testing, Sensitivity and specificity analysis, Gene burden testing (extensive use and design), Sequence kernel association testing, GWAS stats, Pathogen variation stats, Dimension reduction, PCA, SVD, Population structure and stats, Genome to genome assoc statistics, Prediction modeling with multimodal data for pre-emptive intervention; Model design, Statistical automation and reproducibility, Data summary, Statistical programming in R.

Immunology

Innate and adaptive; Primary immunodeficiencies and autoinflammatory disease; Functional and computational immunology; Host-pathogen interaction; Clinical interpretation; Immunogenomics and pharmacogenomics.

Programming

R, bash, a wide range of Unix/Linux command-line tools, git version control, server-side editing, web-hosting, html, CSS, Java, Ruby, active interest in learning other popular tools; Go, Julia, SQL etc. High performance computing scheduling, learning scalability with cloud-genomics; AWS, Azure, WDL, Cromwell, Dragon.

Data visualisation

Presentation of data to both scientific and lay audiences. Genomic analysis gallery.

Democratized genomics

I work on additional research problems to provide analysis where it is not available from national services, via LawlessGenomics.com (non-diagnostic for referral to clinical genetics). I am also building both the front-end and back-end on AWS for my GATK WGS pipeline including interactive evidence report with ∼150 database scores (e.g. gnomAD, ClinVar, ClinGen, UniProt, GO, OMIM, pathogenicity predictors, ACMG reporting standards, etc.)

SARSCoV2variants.com - Open-source tracking for emerging SARS-CoV-2 variants that pose a risk based on COVID-19 vaccine genetics.

Cell biology

Strong background in wet-lab experimentation and design.

  • In vitro and in vivo models, cell lines from human, animal, cancer, primary cell models, PBMC purification and culture, murine models, animal handling, microbiology, virology.
  • Cancer immunology
  • A wide range of molecular assays; protein expression, ELISA, western blot, histology, immunohistochemistry, immunofluorescence, flow cytometry, FACS, immune biomarkers, cloning, plasmid construction, protein expression, mutagenesis, virology.
  • DNA/RNA/cDNA, purification from blood, hair follicle, saliva/buccol, FFPE, tumor, RT-PCR, RT-qPCR , Sanger seq and primer design.
  • Capture library design, manual library preparation of genomic DNA, massively parallel somatic sequencing, methylation assays, multiple sequencing platforms, clinical cohort design, gene panel design.

Student Supervision

Supervised 5 MSc and several BSc student projects, MSc coursework supervision, BSc coursework supervision.

2021 MSc. Gene burden testing methods for susceptibility to infection.

2021 MSc. Host genomic analysis of respiratory syncytial virus infection.

2019 MSc. Rare genetic variants associated with sepsis in intensive care.

2019 MSc. Protein network analysis of genetic susceptibility to viral infection.

2017 MSc. Ultra-deep sequencing for somatic variant discovery.

Publications & pre-prints

[11] eLife. Biallelic mutations in calcium release activated channel regulator 2A (CRACR2A) cause a primary immunodeficiency disorder. 10.7554/elife.72559. Beibei Wu, Laura Rice, Jennifer Shrimpton, \textbf{Dylan Lawless}, et al.

[10] Scientific reports. The influence of human genetic variation on Epstein–Barr virus sequence diversity. 10.1038/s41598-021-84070-7 Sina Rüeger, Christian Hammer, Alexis Loetscher, Paul J. McLaren, Dylan Lawless, Olivier Naret, Daniel P. Depledge, Sofia Morfopoulou, Judith Breuer, Evgeny Zdobnov, Jacques Fellay & the Swiss HIV Cohort Study.

[9] Arthritis & Rheumatology. A novel RELA truncating mutation in familial Behçet’s Disease-like mucocutaneous ulcerative condition 10.1002/art.41531. Fahd Adeeb Emma R. Dorris Niamh E. Morgan, Dylan Lawless, et. al.

[8] Blood. Germline TET2 Loss-Of-Function Causes Childhood Immunodeficiency and Lymphoma. 10.1182/blood.2020005844 Jarmila Stremenova Spegarova, and Dylan Lawless, et. al. (Shared first authors).

[7] Journal of clinical immunology. Expanding Clinical Phenotype and Novel Insights into the Pathogenesis of ICOS Deficiency. 10.1007/s10875-019-00735-z Hassan Abolhassani, Yasser M. El-Sherbiny, Gururaj Arumugakani, Clive Carter, Stephen Richards, Dylan Lawless, Philip Wood, Matthew Buckland, Marzieh Heydarzadeh, Asghar Aghamohammadi, Sophie Hambleton, Lennart Hammarström, Siobhan O Burns, Rainer Doffinger & Sinisa Savic.

2019.RAG.pdf

2019 Aug

[6] Journal of Clinical Immunology. Predicting the occurrence of variants in RAG1 and RAG2. 10.1007%2Fs10875-019-00670-z Dylan Lawless, Hana Lango Allen, James Thaventhiran, NIHR Bio-Resource–Rare Diseases Consortium, Flavia Hodel, Rashida Anwar, Jacques Fellay, Jolan E. Walter, Sinisa Savic.

[5] Frontiers in Immunology. A case of AOSD caused by a novel splicing mutation in TNFAIP3 successfully treated with tocilizumab. 10.3389/fimmu.2018.01527 D. Lawless, S. Pathak, T. Scambler, L. Ouboussand, R. Anwar, and S. Savic.

2018.RAG.pdf

2018 Feb

[4] Journal of Allergy and Clinical Immunology. Prevalence and clinical challenges among adult PID patients with recombination-activating gene deficiency. 10.1016/j.jaci.2018.02.007 Dylan Lawless, Christoph B Geier, Jocelyn R Farmer, Hana Allen Lango, Daniel Thwaites, Faranaz Atschekzei, Matthew Brown, David Buchbinder, Siobhan O Burns, Manish J Butte, et al.

[3] Blood. A novel RAG1 mutation reveals a critical in vivo role for HMGB1/2 during V(D)J recombination. 10.1182/blood-2018-07-866939 Daniel Thwaites, Clive Carter, Dylan Lawless, Sinisa Savic, and Joan Boyes.

[2] Journal of Clinical Immunology. Bialellic Mutations in Tetratricopeptide Repeat Domain 7A (TTC7A) Cause Common Variable Immunodeficiency-Like Phenotype with Enteropathy. 10.1007/s10875-017-0427-1 Dylan Lawless, Anoop Mistry, Philip M. Wood, Jens Stahlschmidt, Gururaj Arumugakani, Mark Hull, David Parry, Rashida Anwar, et al

[1] Science Translational Medicine. Familial autoinflammation with neutro- philic dermatosis reveals a regulatory mechanism of pyrin activation. 10.1126/scitranslmed.aaf1471 Seth L. Masters, Vasiliki Lagou, Isabelle J ́eru, Paul J. Baker, Lien Van Eyck, David A. Parry, Dylan Lawless, et al.