Lines in Manga Studio, colors in SAI. Also, go play Analogue: A Hate Story if you haven't already. It's about the smartest visual novel I've played yet. Though admittedly, I haven't played that many. I think the last one I played was about an angel who's sent undercover into a high school to catch a demon who steals breast milk, except she falls out of a tree onto the main character and gets amnesia. Then when they get to school, she finds out that it's an all-nudist school. You can probably guess where things go from there. It's not a pretty scene.