Aspects of the present invention relate at least in part to identification of regions within the genome that are sensitive to a condition. Particularly, although not exclusively, embodiments of the present invention relate to a method and system for identifying regions of the genome where DNA protection from digestion changes in response to a condition, e.g. the nucleosomal organisation is different as compared to a genomic region in a subject without the condition. The condition may be a pathological disorder e.g. cancer, or a variation of a healthy state e.g. depending on person's lifestyle or age. In certain embodiments, the method and systems may identify regions within the genome which differ in patients with sub-sets of the same condition. Aspects of the present invention comprise identification, stratification and monitoring of subjects suffering from a condition by sequencing predetermined regions of a genome.

Aspects of the present invention relate at least in part to identification of regions within the genome that are sensitive to a condition. Particularly, although not exclusively, embodiments of the present invention relate to a method and system for identifying regions of the genome where DNA protection from digestion changes in response to a condition, e.g. the nucleosomal organisation is different as compared to a genomic region in a subject without the condition. The condition may be a pathological disorder e.g. cancer, or a variation of a healthy state e.g. depending on person's lifestyle or age. In certain embodiments, the method and systems may identify regions within the genome which differ in patients with sub-sets of the same condition. Aspects of the present invention comprise identification, stratification and monitoring of subjects suffering from a condition by sequencing predetermined regions of a genome.

A method for hepatocellular carcinoma (HCC) subtype classification and treatment may include identifying, for a liver epithelial cell lineage, one or more features associated with the liver epithelial cell lineage. The one or more features may be designated as representative of a molecular subtype associated with hepatocellular carcinoma (HCC) such as, for example, a cholangio-like subtype, a hepatocyte-like subtype, or a progenitor-like subtype. A patient may be determined to exhibit the molecular subtype if these features are detected within the tumor sample of the patient. Moreover, treatment for the patient may be determined based on the molecular subtype exhibited by the patient. For example, treatment for the patient may include additional therapies, such as an GPC3/CD3 bi-specific antibody, to overcome subtype-specific resistance to combination immunotherapy associated with the progenitor-like subtype. Related systems and computer program products are also provided.

A method for hepatocellular carcinoma (HCC) subtype classification and treatment may include identifying, for a liver epithelial cell lineage, one or more features associated with the liver epithelial cell lineage. The one or more features may be designated as representative of a molecular subtype associated with hepatocellular carcinoma (HCC) such as, for example, a cholangio-like subtype, a hepatocyte-like subtype, or a progenitor-like subtype. A patient may be determined to exhibit the molecular subtype if these features are detected within the tumor sample of the patient. Moreover, treatment for the patient may be determined based on the molecular subtype exhibited by the patient. For example, treatment for the patient may include additional therapies, such as an GPC3/CD3 bi-specific antibody, to overcome subtype-specific resistance to combination immunotherapy associated with the progenitor-like subtype. Related systems and computer program products are also provided.

Provided herein are methods of treating a patient afflicted with a tumor according to the tumor's microenvironments (TME). Also provided are gene panels that can be used for identifying a human subject afflicted with a cancer suitable for treatment with a particular therapeutic agent based on the subject's TME.