Metadata supporting the article: Association between the nucleosome footprint profile of plasma cell-free DNA and response to neoadjuvant chemotherapy for breast cancer
Creators: name: Yang, Xu
name: Cai, Geng-Xi
name: Han, Bo-Wei
name: Guo, Zhi-Wei
name: Wu, Ying-Song
name: Lyu, Xiaoming
name: Huang, Li-Min
name: Zhang, Yuan-Bin
name: Li, Xin
name: Ye, Guo-Lin
name: Yang, Xue-Xi
Publisher: name: figshare
Year: 2021
Subjects: Biological Techniques
Cancer
Medicine
Cancer Genetics
Chemotherapy
Gene Expression (incl. Microarray and other genome-wide approaches)

description: Gene expression signatures have been used
to predict the outcome of chemotherapy for breast cancer. The nucleosome
footprint of cell-free DNA (cfDNA) carries gene expression information of the
original tissues and thus may be used to predict the response to chemotherapy.
In this study, the authors carried out the nucleosome positioning on cfDNA from
85 breast cancer patients and 85 healthy individuals and two cancer cell lines
T-47D and MDA-MB-231 using low-coverage whole-genome sequencing (LCWGS) method.
 In order to identify the footprints of
cfDNAs corresponding with the responses to neoadjuvant chemotherapy in
patients, the authors mapped on nucleosome positions on cfDNAs of patients with
different responses: responders (pretreatment, <i>n </i>= 28; post-1 cycle, post-3/4
cycles, and post-8 cycles of treatment, <i>n </i>= 12) and nonresponders
(pretreatment, <i>n </i>= 10; post-1 cycle, post-3/4 cycles, and post-8 cycles
of treatment, <i>n </i>= 10).<br>

<b>Data access: </b>All novel
sequencing datasets (cfDNA whole-genome sequencing, MNase sequencing and mRNA sequencing)
generated during this study, are publicly available in Sequence Read Archive: https://identifiers.org/ncbi/insdc.sra:SRP302308.
All other datasets generated and analysed during the study, are available in
the figshare repository: https://doi.org/10.6084/m9.figshare.13709953. Data supporting
figures 5A, 5D and figures 6-8, are included in the supplementary tables that
accompany the article.<br>

<b>Study approval and
patient consent</b>: Ethical approval for the study was received
from the Ethics Committee of the Affiliated Foshan Hospital of Sun Yat-Sen
University. All participants provided written informed consent.<br>

<b>Study
aims and methodology</b>: In present study,
to explore relationships among the cfDNA nucleosome profile, intracellular
nucleosome positioning, and gene expression, the authors used breast cancer
cell line supernatant to mimic plasma cfDNA and sequenced it using
next-generation sequencing (NGS) technology. Simultaneously the cell particles
were subjected to MNase sequencing and mRNA sequencing. The authors analyzed
correlations by comparing the nucleosome footprint profiles 1 kb upstream and 1
kb downstream of transcription start sites (TSSs), in particular at the exact
positions of TSSs. Furthermore, plasma cfDNA footprint profiles were
characterized by low-coverage sequencing, and differences in profiles in
TSS-adjacent regions were analyzed between healthy individuals and patients and
between responders and nonresponders to neoadjuvant epirubicin-cyclophosphamide-docetaxel
chemotherapy. Finally, the authors used plasma collected before and after
treatment to assess correlations between cfDNA footprint profiles and response
to breast cancer treatment and to examine changes in the footprint associated
with treatment.

The
following human breast cancer cell lines were used: T-47D and MDA-MB-231.

The
study included 85 healthy individuals from Guangzhou Darui Biotechnology
company and 30 from the Third Affiliated Hospital of Southern Medical
University, and 145 breast cancer patients from the First People’s Hospital of
Foshan in Guangdong, China.

The
following are described in more detail in the related article: cfDNA
sequencing, MNase sequencing, gene expression sequencing (mRNA sequencing), sequencing read alignment
and processing, TSS profiles of cDNA and MNase sequencing, correlation analyses
of cfDNA-seq, MNase-seq, and RNA-seq data, technical reproducibility assessment,
Procedure of Classifiers Construction, and Functional annotation and enrichment.<br>

<b>Datasets supporting the article</b>: The document <b>Yang, X. et al.xlsx</b> includes a list of all the datasets generated
and analysed during the study, their file formats and links to the data.