How Many Fingers Does a Compound Have? Molecular Similarity beyond Chemical Space

The concept of molecular fingerprints and molecular similarity have matured and found innumerable applications in academia as well as industry, in particular in drug discovery. Chemical similarity is almost too commonplace for us to notice anymore. Still, this powerful concept that molecules can a) be represented in terms of their interesting properties and b) are in one way or another similar to each other has been growing over the past two decades to break out of the confinement of chemical space. Today, we do not just use chemical similarity to find compounds that biologically will behave the same; rather, we directly build on ever growing biological profiles to directly assess bio-similarity. In addition, capturing the rich descriptions of compound-induced phenotypes from literature gives us yet another molecular fingerprint. We define 'molecular fingerprint' to represent properties of compounds that include, but also, go beyond chemical descriptors. This brings new challenges and opportunities such as: How do we define and encode bioactivity and literature profiles in form of comparable fingerprints? How do we deal with the inherent sparseness of such representations? And, most importantly, how do we use these various ways of defining similarity in concert? Network concepts that have emerged and matured in social sciences, such as friend-of-a-friend may be of help - after all, we have been using the concept of "chemical neighborhoods" all along. Here we will present strategies to defining and slicing non-conventional molecular fingerprints as well as the application of network algorithms to build and navigate heterogeneous similarity networks.