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Cambridge Healthtech Institute’s Inaugural

Spatial Biology & Single-Cell Analysis

Adding a New Dimension to Multi-Omic Analysis

February 21-22, 2022


Emerging technologies in spatial biology and single-cell analysis promise to enable better understanding of biological pathways, discovery of new biomarkers and drug targets, and more insightful translational research. Cambridge Healthtech Institute’s Inaugural Spatial Biology & Single-Cell Analysis meeting will explore the latest technologies and research in using spatial multi-omics tools to uncover molecular insights in oncology, neurology, immunology and more.

Monday, February 21

7:00 am Registration Open and Morning Coffee (Indigo West Foyer AB)



7:55 am

Chairperson's Remarks

Daniel T. Chiu, PhD, A. Bruce Montgomery Professor of Chemistry; Endowed Professor in Analytical Chemistry; Professor of Bioengineering, University of Washington
8:00 am

Using Spatial Approaches to Understand the Molecular Pathology of Alzheimer’s Disease

Simon Gregory, PhD, Professor, Neurology and Vice Chair of Research, Duke University; Director, Molecular Genomics Core, Duke Molecular Physiology Institute

Differences in Alzheimer’s disease (AD) susceptibility are observed between brain regions as they accumulate disease related pathology. We have used spatial transcriptome and in situ sequencing to characterize amyloid plaque-related and grey matter expression changes from multiple tissues from a single AD individual. Our spatial approach is providing insight into the mechanisms of AD development and may guide future therapeutic strategies aimed at preventing disease progression.

8:30 am

Multiplex Immunohistochemistry/Immunofluorescence Techniques in the Era of Cancer Immunotherapy

Edwin R. Parra Cuentas, PhD, Assistant Professor, Translational Molecular Pathology, MD Anderson Cancer Center

As the field of cancer immunotherapy advances and new therapeutics are developed, there has been much emphasis on understanding tumor-specific aspects of a patient’s individualized disease, and subsequently targeting treatment towards specific biomarkers. Multiplexed imaging platforms to simultaneously detect multiple markers in a single cell resolution in the same tissue section emerged in the last years as powerful tools to immuno-profiling several tumor tissues and cell-cell interactions which suggest improved diagnostic benefit. Characterize the applicability of these technologies will be important in the field of cancer immunotherapy by helping identify the best options for the application of multiplex technologies.

9:00 am

Multi-Scale Spatial Multi-Omics Profiling for Precision Medicine

Ahmet Coskun, PhD, Assistant Professor, Biomedical Engineering, Georgia Institute of Technology

The spatial organization of cells and subcellular variations in tissues can be considered as a quantitative metric in determining the health and disease states. Single-cell analyses of molecular profiles with in-situ detection methods dissect spatial heterogeneity of distinct cell types. Such detailed cellular maps shed light on spatial regulation mechanisms of diseases. In this talk, I will introduce multiplex imaging modalities (genomics, proteomics, and metabolomics) to quantify up to a hundred markers at macromolecular resolution in single cells for Immuno-engineering, precision oncology, and regenerative medicine applications.

9:30 am Session Break


9:45 am Interactive Discussions (In-person only)

Interactive Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. For in-person events, the facilitator will lead from the front of the room while attendees remain seated to promote social distancing.  To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Interactive Discussion page on the conference website for a complete listing of topics and descriptions.


10:15 am

Building Single-Cell Proteomics Platforms for Therapeutic Discovery

Christopher M. Rose, PhD, Scientist, Microchemistry & Proteomics & Lipidomics, Genentech, Inc.

Unbiased single cell proteomics (SCP) is undergoing a revolution due to the increased sensitivity of mass spectrometers and the increased level of multiplexing within quantitative approaches. Here, we describe the characterization of quantitative accuracy within current approaches to mass spectrometry based single cell proteomics and describe novel data acquisition methods aimed at improving the quality and depth of SCP analyses. We then describe how these methods are being utilized to better understand therapeutically relevant pathways within research and early development.

10:45 am

Unbiased Spatial Analytics and Explanable Artificial Intelligence Powers Precision Medicine Pathology

D. Lansing Taylor, PhD, Distinguished Professor and Allegheny Foundation Professor of Computational & Systems Biology; Director, University of Pittsburgh Drug Discovery Institute
11:15 am

Microscopy-Based Functional Single-Cell Profiling

Miao-Ping Chien, PhD, Principal Investigator, Oncode Institute, Molecular Genetics, Erasmus University

Our lab has developed microscopy-based functional single-cell sequencing(FUNseq) and analysis technologies, which can be applied to subtype heterogeneous populations of cells and link tumorigenic phenotypes to causative genotypes. FUNseq can be combined with single-cell genome, transcriptome, and proteome profiling. FUNseq has been exploited to identify driving pathways related to aggressive migration in different (patient-derived) tumors and to profile subpopulations of cancer cells displaying chromosomal instability or abnormal DNA damage response.

Jason Kim, Senior Science & Technology Advisor, 10x Genomics

10x Genomics Chromium Single Cell products enable molecular profiling with multiomic capabilities in hundreds of thousands of single cells, and our Visium Spatial products provide a comprehensive understanding of the relationships between cellular function, phenotype, and location in intact tissue sections. Join us to learn how you can uncover molecular insights, dissect cell-type differences, detect novel cell subtypes and biomarkers, define gene regulatory interactions, and decipher spatiotemporal gene expression patterns.

12:15 pm Session Break
Lakshmi Chandramohan, PhD (ABMM), Principal Scientist, Associate Director, Molecular Assay Services, Pharma Services, NeoGenomics Laboratories

We applied a multi-faceted, highly multiplexed tissue analysis approach to quantitate and characterize spatial arrangement of key IO protein markers in a solid tumor cohort using GeoMxTM DSP and MultiOmyxTM Immunofluorescence. Direct correlation was observed for eight out of 10 IO markers between DSP counts and MultiOmyx positive cell densities. This study showed that integrated analysis by both technologies provides a comprehensive understanding of the immune landscape in oncology FFPE tissues.

12:50 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:20 pm Session Break


Jason Kim, Senior Science & Technology Advisor, 10x Genomics
1:35 pm

Single-Cell Spatial Analysis of Single-Stranded DNA Using Light-Assisted in situ DNA Synthesized

James Eberwine, PhD, Elmer Holmes Bobst Professor, Systems Pharmacology and Translational Therapeutics; Co-Director, Penn Program in Single Cell Biology; Co-Director, Penn Center for Subcellular Biology, University of Pennsylvania Perelman School of Medicine

Genomic DNA transitions between single-stranded and double-stranded states during transcription, DNA repair and replication. This interconversion is critical to the maintenance of cellular homeostasis and plasticity. To assess the single-stranded DNA chromatin landscape at the level of a single cell, we have developed spatially light-activated CHEX-seq (CHromatin EXposed) that utilizes our in situ transcription technology, for identifying the non-B-form single-stranded open chromatin in situ in individual, formalin-fixed cells. 

2:05 pm

New Fluorescent Reagents to Enable Spatial Biology

Daniel T. Chiu, PhD, A. Bruce Montgomery Professor of Chemistry; Endowed Professor in Analytical Chemistry; Professor of Bioengineering, University of Washington

Fluorescence-based techniques have become an indispensable tool kit in both basic cellular studies and in vitro diagnostics. However, the intrinsic limitations of conventional dyes, such as short Stoke’s shift and low absorptivity, have posed difficulties for advancing highly multiplexed assays. We have developed a new class of fluorescent probes called Pdots, and this talk will highlight their development to enable high multiplex single-cell analysis and spatial biology.

2:35 pm

AI-Enabled, Label-Free Single-Cell Spatial Biology Technologies with Image-Guided FACS

Yuhwa Lo, PhD, Professor, Electrical & Computer Engineering, University of California, San Diego

We will discuss the application of image-guided single-cell sorter to recognize and isolate cell types and intracellular cellular features. Image-guided sorter can generate a very large amount of cell images with high resolution and throughput. Applying artificial intelligence with CNN, we show that rich information can be obtained to produce insight in cell types, behaviors, and health. The ability to isolate cells for verification helps the semi-supervised deep-learning system improve its performance.

Thomas Campbell, PhD, Product Manager, Canopy Biosciences - A Bruker Company

Understanding the spatial distribution of immune cell populations is critical in advancing our understanding of cancer.  Here we present the analysis of tissue samples using ChipCytometry, which combines iterative immuno-fluorescent staining with high-dynamic range imaging to facilitate quantitative phenotyping with single-cell resolution. Standard FCS files are generated from multichannel images, enabling quantification of dozens of protein biomarkers and accurate identification of cellular phenotypes via flow cytometry-like gating. 

3:20 pm Sponsored Presentation (Opportunity Available)
3:35 pm Session Break



4:15 pm

Chairperson's Remarks

Robert C. Green, MD, MPH, Professor and Director of Genomes2People Research, Mass General Brigham, Broad Institute, Ariadne Labs and Harvard Medical School
Stephen Williams, MD, PhD, CMO, SomaLogic

Reliable outcomes prediction enables increased power in clinical trials and improved allocation of resources in clinical practice. The new discipline of using highly multiplexed measurements, machine learning and mixed study populations can lead to robust and generalized predictors of catastrophic and near-term risks. Key examples using SomaScan® proteomics for cardiovascular events, heart failure mortality and loss of kidney function will be shown.

4:30 pm

Universal Newborn Sequencing and the Path to Preventive Genomics

Robert C. Green, MD, MPH, Professor and Director of Genomes2People Research, Mass General Brigham, Broad Institute, Ariadne Labs and Harvard Medical School

Twenty years after the completion of the Human Genome Project, there is beginning to be broad acceptance for returning actionable genomic findings as an ethical imperative in large-scale genomic research, as secondary findings in indication-based sequencing, and as population-scale screening in forward-looking healthcare systems. While the evident data on patient-provider acceptability, clinical utility and cost-benefit are far from comprehensive, empirical research from many domains suggest that when unanticipated genomic information is delivered, patients are deeply interested and do not experience unusual distress, providers can manage disclosure and care with appropriate support, and downstream healthcare utilization is modest and appropriate. We recently completed the first randomized trial of comprehensive genome sequencing in healthy newborns and are beginning a multi-site second phase of this research (the NIH funded BabySeq Project). We present data from this and other studies to suggest that universal newborn sequencing may be well-tolerated and cost-effective, and may soon provide a platform for the lifelong use of genomics in risk stratification, disease mitigation and expanding longevity.

5:00 pm

Transforming Genomic Healthcare in the United Kingdom

Sir Mark Caulfield, PhD, Professor & Director, Clinical Pharmacology, The William Harvey Research Institute, Queen Mary University of London; CEO, Barts Life Sciences

The 100,000 Genomes Project focused on rare disease, cancer, and infection and demonstrated the potential of whole genomes to uplift diagnoses by 25% in rare disease, have a clinical utility for 25% of cancer patients, and discover 15 novel gene loci for severe COVID-19. Exploring of pharmacogenomics reveals many of us have genetic variants which if paired with a drug may cause harm. To do this we created a new National Test Directory where we evaluated 300,000 tests upgraded 25% to new technologies, and 500,000 whole genomes are available for rare disease and cancer care over the next 5 years. We have used this to transform the National Health Service with a new Genomic Medicine Service offering equitable access to 56 million people.

5:30 pm

Precision Health: Closing the Information and Decision Gaps

Jessica L. Mega, MD, MPH, Co-Founder and Chief Medical & Scientific Officer, Verily; Adjunct Professor, Stanford University School of Medicine

Genomic insights have proven to be powerful, from providing a better interpretation of the pathobiology of disease to tailoring medications based on pharmacogenetics. At the same time, there has been a growing appreciation that a multitude of inputs are needed to provide a comprehensive understanding of both the health of an individual and how it relates to the broader population. Accounting for (1) the highly complex interplay of biological, behavioral, environmental, and social systems, and (2) the changes in the cadence of data collection from episodic to continuous will be critical to improving clinical outcomes. The scale of data, from gigabytes to terabytes per individual, necessitates an updated framework to collect, organize, and activate this rich health information; recent advances in biomedical information systems and computation are making these activities possible. Additionally, tools to harness more comprehensive biological insights are being developed, and people are interacting more directly with their health data, along with the support of researchers and clinicians. All these efforts to close the information and decision gaps will ultimately advance precision health.


Precision Health: Convergence of Genomics, Digital MedTech and Healthcare

Panel Moderator:
Robert C. Green, MD, MPH, Professor and Director of Genomes2People Research, Mass General Brigham, Broad Institute, Ariadne Labs and Harvard Medical School

Precision Health promises a much-needed shift from “sick-care” to “healthcare.” Driven by innovations in genomics, medtech, and AI, precision health strategies can focus on prediction, prevention, and early detection for individualized health and wellness. The panel will discuss how genomics and digital health technologies can advance community-wide genetic screening and early disease detection, patient monitoring and preventative health strategies, personalized lifestyle and wellness approaches, and precision health equity.

Sir Mark Caulfield, PhD, Professor & Director, Clinical Pharmacology, The William Harvey Research Institute, Queen Mary University of London; CEO, Barts Life Sciences
Jessica L. Mega, MD, MPH, Co-Founder and Chief Medical & Scientific Officer, Verily; Adjunct Professor, Stanford University School of Medicine
Lara Jehi, MD, Chief Research Information Officer, Professor, Neurology, Cleveland Clinic
Megan Mahoney, MD, Clinical Professor, Primary Care & Population Health, Stanford University
6:30 pm Welcome Reception in the Exhibit Hall with Poster Viewing (Indigo BFGCDH)
7:30 pm Close of Day

Tuesday, February 22

7:30 am Registration Open and Morning Coffee (Indigo West Foyer AB)



8:00 am

Single-Cell and Spatial Genomics for Next-Generation Neuropathology

Evan Macosko, PhD, Assistant Professor, Psychiatry, Stanley Center for Psychiatric Research, Broad Institute

For decades, neuropathological tissue analysis has been hypothesis-driven: genes or pathways are nominated by experimental models, and then tested in human samples. However, single cell and spatial genomics technologies enable much more detailed characterization of tissue, allowing us to build disease hypotheses directly from the human tissue itself. In this talk I will describe our technology development in single-cell (Drop-seq) and spatial genomics (Slide-seq) and our application to Parkinson's disease.

8:30 am

Comprehensive Integration of Single-Cell and Spatial Transcriptomic for Mapping Human Tissue Architecture

Omer Bayraktar, PhD, Group Leader, Wellcome Sanger Institute

Spatial transcriptomic technologies promise to resolve cellular wiring diagrams of tissues in health and disease, but comprehensive mapping of cell types in situ remains a challenge. We present сell2location, a principled Bayesian model that can resolve fine-grained cell types in spatial transcriptomic data and create comprehensive cellular maps of diverse tissues. We comprehensively assess cell2location in three different tissues and consistently demonstrate improved mapping of fine-grained cell types. Cell2location provides as a versatile first-line analysis tool for mapping tissue architectures in a comprehensive manner.

Charlie Roco, PhD, CTO, Parse Biosciences

Single-cell experiments are rapidly evolving to embrace scale following the introduction of a commercial solution that enables up to 1 million cells at a time. Cohorts and replicates simplified for cost or assay compatibility are being pursued ambitiously. This rapid expansion has highlighted opportunities for more effective single-cell research at scale. This session explores historical considerations and highlights effective strategies to embrace this newfound power.

9:30 am Coffee Break in the Exhibit Hall with Poster Viewing (Indigo BFGCDH)
10:10 am

Next-Generation Tools for Spatial Genomics

Fei Chen, PhD, Assistant Professor, Stem Cell & Regenerative Biology, Broad Institute

The precise spatial localization of molecular signals within tissues richly informs the mechanisms of tissue formation and function. Here, we’ll introduce Slide-seq, a technology which enables transcriptome-wide measurements with near-single cell spatial resolution. We’ll describe recent experimental and computational advances to enable Slide-seq in biological contexts in biological contexts where high detection sensitivity is important. More broadly, we’ll discuss the promise and challenges of spatial transcriptomics for tissue genomics.

10:40 am

Integrating Single-Cell and Spatial Transcriptomics for In-Depth Patient Tissue Interrogation

Ioannis Vlachos, PhD, Assistant Professor & Co-Director, Bioinformatics, Cancer Research Institute, Beth Israel Deaconess Medical Center

Spatial technologies have started to revolutionize our ability to deeply interrogate tissue and capture layers of information which were not previously possible. During this talk, I will provide an overview of our efforts to seamlessly integrate spatial transcriptomics with single nucleus sequencing to capture cellular and transcriptional alterations observed in human pathologies, with an emphasis on an extensive collaborative project focusing on COVID-19 phenotypes.

11:10 am Sponsored Presentation (Opportunity Available)
11:40 am Session Break
11:50 am Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
12:20 pm Refreshment Break in the Exhibit Hall with Poster Viewing (Indigo BFGCDH)
1:00 pm Close of Spatial Biology & Single-Cell Analysis Conference

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