# Molecular images and machine learning to extract placental function from maternal cfDNA

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $591,753

## Abstract

Abstract
 Circulating cell free DNA (cfDNA) has revolutionized prenatal diagnostics, but this is the tip of the
iceberg, as cfDNA fragmentation patterns embed epigenetic footprints indicative of cell of origin, cellular
function and pathological state. cfDNA is fragmented with sizes centered around 145bp and 166bp which is
approximately the length of DNA wrapped around a nucleosome, and a nucleosome plus its linker,
respectively. Shorter fragments (30-100bp) also exist and have a clear periodicity of 10bp, corresponding to a
turn of the DNA helix wrapped around the core histone. Recent reports have shown that the fragmentation
sizes of cfDNA are tissue specific, which is a product of distinct nucleosome spacing that is inherent in the
function of individual tissues. When these individual fragments are compared with existing epigenetic data from
tissues, they can be binned into cell of origin simply based on whether they reveal the nucleosome positioning
information of the originating tissue. Identifying cfDNA fragments of placental origin from maternal
circulation would provide a non-invasive means of assessing placental function during human
pregnancy.
 Several major barriers inhibit cfDNA as a non-invasive method for examining placental function: 1) the
ability to accurately identify the placental origin of the short <160bp cfDNA fragments that constitute regulatory
information (paternal SNPs occur at frequency of approximately 1/2000bp). 2) the ability to use these
fragments to piece together precise epigenetic states of the placenta. 3) the cost of deep whole genome
sequencing that has traditionally been required to deconvolute epigenetic profiles of admixed cellular origins.
Our goal is to overcome each of these barriers by exploiting state-of-the-art genomics and machine learning
techniques to extract precise information about human placental function from cfDNA. We will first compile
robust and accurate nucleosome information, including epigenetic and transcription factor occupancy, from the
human placenta and then we will establish machine-learning platforms to elucidate placental cfDNA from
maternal circulation at low cost. Success in this project will enable earlier intervention for high-risk
pregnancies and facilitate the longitudinal, non-invasive real-time monitoring of pregnancy
progression, thereby informing adaptive treatment decision-making.

## Key facts

- **NIH application ID:** 10114907
- **Project number:** 5R01HD094513-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Julie C Baker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $591,753
- **Award type:** 5
- **Project period:** 2018-03-20 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114907

## Citation

> US National Institutes of Health, RePORTER application 10114907, Molecular images and machine learning to extract placental function from maternal cfDNA (5R01HD094513-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10114907. Licensed CC0.

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