Single-Cell Sequencing 101: DNA & Multi-Omics For Precision Medicine

Complex and elusive, cancer has been the focus of intense research for decades. A major challenge to defeating cancer is its continual evolution and inherent heterogeneity. Each tumor is a unique melting pot of clones that harbor different sets of mutations, and this variation has significant implications for how tumors grow and respond to therapy. For instance, the presence of a few cells that are resistant to treatment can bring about relapse after a tumor has been seemingly eradicated. Thus, characterizing the underlying clonal architecture of tumors is key to developing cures.

Delving deeper into cancer requires a progressive approach that preserves the resolution of each cell. Currently, most clinics rely on bulk NGS metrics that average mutation frequencies across a tumor sample. Using these measurements to determine clonal structure is severely limited and based on inference. To truly uncover the complexity of cancer, we need a “more powerful microscope”.

Fortunately, innovations in single-cell technologies have enabled us to peer deeper into cancer with unprecedented resolution and sensitivity. With single-cell DNA sequencing (scDNA-seq), the genetic structure of tumors can be fully resolved. Furthermore, powerful single-cell multi-omics can now correlate genotype and immunophenotype — enabling the comprehensive characterizations of tumor cells. These innovations have particular promise in the translational space, where fundamental research on cancer complexity can directly inform actions in the clinic. Additionally, single-cell analyses can accelerate current pharmacological workflows, such as those for cell and gene therapies. With the ability to obtain genotype and phenotype information in a cell-specific manner, the era of single-cell ‘omics has opened the door to a “resolution revolution.”

In this eBook, we explore how single-cell DNA sequencing and multi-omics are rapidly elevating how cancer is both studied and treated. These technologies are being quickly adopted in the hematological oncology field, as liquid tumors are easier to sample and study over time. While most of our examples involve heme malignancies, we also discuss the development of this technology for solid tumors.