Workstreams

Alliance Workstreams are responsible for realizing the goals of the Alliance in key areas by setting standards, providing tools and disseminating information.

Clinical Variant Interpretation (CVI)

CVI Strategic ROADMAP

ABOUT: The Clinical Variant Interpretation (CVI) workstream resolves issues relating to the use of MAVE data to interpret human genetic variants. Members of this team:

  • Develop approaches for integrating variant effect maps with other sources of information in clinical interpretation

  • Establish best practices for evaluating/benchmarking clinical utility of variant effect maps

  • Exemplify use of variant effect maps in diagnostic practice

WORKSTREAM LEAD(S): Lea Starita (BBI/UW) and Clare Turnbull (ICR)

Contributors/ Members:

Rocio Acuna-Hidalgo (Nostos Genomics)
Jonathan Sanford Berg (UNC School of Medicine)
Jeffrey Calhoun (Northwestern University)
Sali Farhan (McGill University)
Sujatha Jagannathan (University of Colorado, Anschutz Medical Center)
Rachel Karchin (Johns Hopkins University)
Tina Pesaran (Ambry Genetics)
Elizabeth Radford (Cambridge University / Wellcome Sanger Institute)
Fritz Roth (University of Pittsburgh and University of Toronto)
Alan Rubin (Walter and Eliza Hall Institute of Medical Research | WEHI)
Brian Shirts (University of Washington)
Amanda Spurdle (QIMR Berghofer MRI)
Alex Wagner (Nationwide Children’s Hospital)
San Ming Wang (University of Macau)
Rehan Villani (QIMR Berghofer MRI)
Charlie Rowlands (Institute of Cancer Research)
Sophie Allen (Institute of Cancer Research)
Fergus Couch (Mayo Clinic)

Data Coordination and Dissemination (DCD)

DCD Strategic ROADMAP

ABOUT: The Data Coordination and Dissemination (DCD) workstream facilitates the sharing and discoverability of MAVE projects and MAVE data.

Members of this workstream may:

  • Engage with clinical and non-clinical data resources and providers to enable MAVE data sharing, including federation with other resources identified by data consumers (e.g. ClinGen, UniProt, PharmGKB)

  • Define and promote standards and infrastructure for MAVE data deposition, coordination and dissemination

  • Define and promote infrastructure for data deposition, coordination and dissemination

  • Write review, recommendation or guideline papers, often in conjunction with other AVE work streams

  • Oversee the growth and management of MaveDB

WORKSTREAM LEAD: Alan Rubin (WEHI) and Julia Foreman (DECIPHER, EMBL-EBI)

Contributors/ Members:
Jeremy Arbesfeld (Nationwide Children’s Hospital, Wagner Lab) 
Carol Bult (The Jackson Laboratory)
Melissa Cline (UC Santa Cruz)
Erwan Delage (Wellcome Sanger Institute)
Helen Firth (Newnham College, Cambridge)
Sarah Hunt (Ensembl)
Sumaiya Iqbal (Broad Institute)
Rachid Karam (Ambry Genetics)
Shannon McNulty (UNC)
Kevin Riehle (ClinGen)
James Stephenson (EMBL-EBI)
Alex Wagner (Nationwide Children’s Hospital; GA4GH)
Andy Yates (EMBL-EBI)

There is an Open Call for New Members (DCD workstream) (Deadline to submit an application and indicate your interest in joining has been extended to Jan 31st, 2025).

Experimental Technology and Standards (ETS)

ETS Strategic ROADMAP

This workstream facilitates the development, scaling, evaluation, comparison and dissemination of new MAVE methods. Members of this team:

  • Develop measures by which to evaluate experimental methods, e.g., what information should go on a ‘report card’ for a mutagenized library, a transfection step, a flow-sorting experiment.

  • Develop an information resource for alternative technologies with protocols, tips, caveats.

  • Design physical standards (mutagenized libraries, barcode libraries, gRNA pools) that can enable controlled comparison of other tech steps, and strategies for sharing physical standards across groups.

WORKSTREAM LEAD(S): Andrew Glazer (VUMC) and Alex Nguyen Ba (University of Toronto)

Contributors/ Members:
Victoria Nicole Parikh (Stanford University) previous co-chair
Melina Claussnitzer (Harvard, Broad Institute) previous co-chair
Fritz Roth (University of Toronto) previous co-chair
Benedetta Bolognesi (IBEC) previous co-chair
Greg Findlay (Francis Crick Institute)
Jacob Kitzman (University of Michigan)
Daniel Tabet (University of Toronto)
Michael Böttcher (Martin Luther University)
Kenneth Matreyek (Case Western)
Valeria Vasta (University of Washington)
Sven Diederichs (DKFZ | University Hospital Freiburg)
Guillaume Diss (Friedrich Miescher Institute)
Andrea Martella (AstraZeneca)
Daniel O’Neill (AstraZeneca)

Analysis, Modelling and Prediction (AMP)

AMP Strategic ROADMAP

The Analysis, Modelling and Prediction (AMP) workstream (formerly known as Variant Scoring Tools and Methods) will develop strategies to assess variant scoring, error estimation and visualization methods. AMP will evaluate the impact of experimental design choices like library complexity, number of independent cells and sequencing depth on the accuracy of scoring and error estimation. AMP will also be responsible for developing reporting standards to enable evaluation of the quality of MAVE datasets in terms of internal controls, replicability and minimal information to be included.

Members of this workstream:

  • Assess alternative methods for primary data analysis and visualization, e.g. to go from barcode counts to variant scores and error estimates to generate viewable variant effect maps

  • Develop strategies to evaluate primary analysis methods, e.g., replication between groups, or comparison with population allele frequencies or computational predictors.

  • Evaluate the impact of experimental design choices (e.g., library complexity, number of independent cells) on the validity of scores and error estimates.

WORKSTREAM LEAD(S): Joseph Marsh (University of Edinburgh)

Contributors/ Members:
Kresten Lindorff-Larsen (Copenhagen University)
David McCandlish (Cold Spring Harbor Laboratory)
Mafalda Dias (CRG)
Jonathan Frazer (CRG)
Justin Kinney (Cold Spring Harbor Laboratory)
Juannan Zhou (University of Florida)
Fabrizio Pucci (Université Libre de Bruxelles)
Jimmie Ye (UC San Francisco)
Sushant Kumar (University of Toronto)
Victoria Offord (Wellcome Sanger Institute)
Rose Orenbuch (Harvard Medical School)
Courtney Shearer (Harvard University)
Kyriaki Michailidou (Cyprus Institute of Neurology and Genetics)

Learn more about our workstream and committee chairs here: https://www.varianteffect.org/chairs