What Is Perturbation Space for a Virtual Cell?

Fabian Theis calls perturbation space the input space of everything that happens to a cell. A virtual cell model should take the whole space, including combinations, because the inputs influence cell state. He is unsure whether disease and time belong on that list as well.

A full gene knockout is only the hardcore end. Most influences are subtler, though taking pieces out still helps explain the system. In ordinary development and in homeostasis, cells live in complex multicellular states and talk to each other all the time. A neighbor, a signaling gradient, or hormones coming in all count, and much of that outside input cannot be tuned up or down. In dish-based drug screens, changing media conditions has a large impact. The cocktails people invent can turn skin cells into embryo-like cells and then into new cells for healing the body. Yamanaka factors, Nobel laureate work, are one famous case. Gene-level inputs run from a full knockout to subtler human genetics, and the space of things you can do to a cell is rich enough to cover all of it.