Health & Bioscience
Research in health and biomedical sciences has a unique potential to improve peoples’ lives, and includes work ranging from basic science that aims to understand biology, to diagnosing individuals’ diseases, to epidemiological studies of whole populations. We recognize that our strengths in machine learning, large-scale computing, and human-computer interaction can help accelerate the progress of research in this space. By collaborating with world-class institutions and researchers and engaging in both early-stage research and late-stage work, we hope to help people live healthier, longer, and more productive lives.
Recent Publications
Accurate human genome analysis with Element Avidity sequencing
Andrew Carroll
Daniel Cook
Lucas Brambrink
Bryan Lajoie
Kelly N. Wiseman
Sophie Billings
Semyon Kruglyak
Bryan R. Lajoie
Junhua Zhao
Shawn E. Levy
Kishwar Shafin
Maria Nattestad
BMC Bioinformatics (2025)
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We investigate the new sequencing technology Avidity from Element Biosciences. We show that Avidity whole genome sequencing matches mapping and variant calling accuracy with Illumina at high coverages (30x-50x) and is noticeably more accurate at lower coverages (20x-30x). We quantify base error rates of Element reads, finding lower error rates, especially in homopolymer and tandem repeat regions. We use Element’s ability to generate paired end sequencing with longer insert sizes than typical short–read sequencing. We show that longer insert sizes result in even higher accuracy, with long insert Element sequencing giving noticeably more accurate genome analyses at all coverages.
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Importance: Interest in artificial intelligence (AI) has reached an all-time high, and health care leaders across the ecosystem are faced with questions about where, when, and how to deploy AI and how to understand its risks, problems, and possibilities.
Observations: While AI as a concept has existed since the 1950s, all AI is not the same. Capabilities and risks of various kinds of AI differ markedly, and on examination 3 epochs of AI emerge. AI 1.0 includes symbolic AI, which attempts to encode human knowledge into computational rules, as well as probabilistic models. The era of AI 2.0 began with deep learning, in which models learn from examples labeled with ground truth. This era brought about many advances both in people’s daily lives and in health care. Deep learning models are task-specific, meaning they do one thing at a time, and they primarily focus on classification and prediction. AI 3.0 is the era of foundation models and generative AI. Models in AI 3.0 have fundamentally new (and potentially transformative) capabilities, as well as new kinds of risks, such as hallucinations. These models can do many different kinds of tasks without being retrained on a new dataset. For example, a simple text instruction will change the model’s behavior. Prompts such as “Write this note for a specialist consultant” and “Write this note for the patient’s mother” will produce markedly different content.
Conclusions and Relevance: Foundation models and generative AI represent a major revolution in AI’s capabilities, ffering tremendous potential to improve care. Health care leaders are making decisions about AI today. While any heuristic omits details and loses nuance, the framework of AI 1.0, 2.0, and 3.0 may be helpful to decision-makers because each epoch has fundamentally different capabilities and risks.
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Given a training data-set $\mathcal{S}$, and a reference data-set $\mathcal{T}$, we design a simple and efficient algorithm to reweigh the loss function such that the limiting distribution of the neural network weights that result from training on $\mathcal{S}$ approaches the limiting distribution that would have resulted by training on $\mathcal{T}$. Such reweighing can be used to correct for Train-Test distribution shift, when we don't have access to the labels of $\mathcal{T}$. It can also be used to perform (soft) multi-criteria optimization on neural nets, when we have access to the labels of $\mathcal{T}$, but $\mathcal{S}$ and $\mathcal{T}$ have few common points.
As a motivating application, we train a graph neural net to recognize small molecule binders to MNK2 (a MAP Kinase, responsible for cell signaling) which are non-binders to MNK1 (a very similar protein), even in the absence of training data common to both data-sets. We are able to tune the reweighing parameters so that overall change in holdout loss is negligible, but the selectivity, i.e., the fraction of top 100 MNK2 binders that are MNK1 non-binders, increases from 54\% to 95\%, as a result of our reweighing.
We expect the algorithm to be applicable in other settings as well, since we prove that when the metric entropy of the input data-sets is bounded, our random sampling based greedy algorithm outputs a close to optimal reweighing, i.e., the two invariant distributions of network weights will be provably close in total variation distance.
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Local read haplotagging enables accurate long-read small variant calling
Daniel Cook
Maria Nattestad
Lucas Brambrink
Brandy McNulty
John E. Gorzynski
Sneha D. Goenka
Euan Ashley
Miten Jain
Karen Miga
Benedict Paten
Andrew Carroll
Kishwar Shafin
Nature Communications (2024)
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Long-read sequencing technology has enabled variant detection in difficult-to-map regions of the genome and enabled rapid genetic diagnosis in clinical settings. Rapidly evolving third-generation sequencing platforms like Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) are introducing newer platforms and data types. It has been demonstrated that variant calling methods based on deep neural networks can use local haplotyping information with long-reads to improve the genotyping accuracy. However, using local haplotype information creates an overhead as variant calling needs to be performed multiple times which ultimately makes it difficult to extend to new data types and platforms as they get introduced. In this work, we have developed a local haplotype approximate method that enables state-of-the-art variant calling performance with multiple sequencing platforms including PacBio Revio system, ONT R10.4 simplex and duplex data. This addition of local haplotype approximation simplifies long-read variant calling with DeepVariant.
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Artificial Intelligence (AI) holds the promise of transforming healthcare by improving patient outcomes, increasing accessibility and efficiency, and decreasing the cost of care. Realizing this vision of a healthier world for everyone everywhere requires partnerships and trust between healthcare systems, clinicians, payers, technology companies, pharmaceutical companies, and governments to drive innovations in machine learning and artificial intelligence to patients. Google is one example of a technology company that is partnering with healthcare systems, clinicians, and researchers to develop technology solutions that will directly improve the lives of patients. In this chapter we share landmark trials of the use of AI in healthcare. We also describe the application of our novel system of organizing information to unify data in electronic health records (EHRs) and bring an integrated view of patient records to clinicians. We discuss our consumer focused innovation in dermatology to help guide search journeys for personalized information about skin conditions. Finally, we share a perspective on how to embed ethics and a concern for all patients into the development of AI.
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Unsupervised representation learning on high-dimensional clinical data improves genomic discovery and prediction
Babak Behsaz
Zachary Ryan Mccaw
Davin Hill
Robert Luben
Dongbing Lai
John Bates
Howard Yang
Tae-Hwi Schwantes-An
Yuchen Zhou
Anthony Khawaja
Andrew Carroll
Brian Hobbs
Michael Cho
Nature Genetics (2024)
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Although high-dimensional clinical data (HDCD) are increasingly available in biobank-scale datasets, their use for genetic discovery remains challenging. Here we introduce an unsupervised deep learning model, Representation Learning for Genetic Discovery on Low-Dimensional Embeddings (REGLE), for discovering associations between genetic variants and HDCD. REGLE leverages variational autoencoders to compute nonlinear disentangled embeddings of HDCD, which become the inputs to genome-wide association studies (GWAS). REGLE can uncover features not captured by existing expert-defined features and enables the creation of accurate disease-specific polygenic risk scores (PRSs) in datasets with very few labeled data. We apply REGLE to perform GWAS on respiratory and circulatory HDCD—spirograms measuring lung function and photoplethysmograms measuring blood volume changes. REGLE replicates known loci while identifying others not previously detected. REGLE are predictive of overall survival, and PRSs constructed from REGLE loci improve disease prediction across multiple biobanks. Overall, REGLE contain clinically relevant information beyond that captured by existing expert-defined features, leading to improved genetic discovery and disease prediction.
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