Player Core Chapter 8: Playing The Game Checks Step 1: Roll D20

Penalties

Penalties work very much like bonuses. You can have circumstance penalties, status penalties, and sometimes even item penalties. Like bonuses of the same type, you take only the worst all of various penalties of a given type. However, you can apply both a bonus and a penalty of the same type on a single roll. For example, if you had a +1 status bonus from an akashic download spell but a –2 status penalty from the sickened condition, you'd apply them both to your roll—so akashic download still helps even though you're feeling unwell.
Unlike bonuses, penalties can also be untyped, in which case they won't be classified as “circumstance,” “item,” or “status.” Unlike other penalties, you always add all your untyped penalties together rather than simply taking the worst one. For instance, when you use attack actions, you incur a multiple attack penalty on each attack you make on your turn after the first attack of the turn, and when you attack a target that's beyond your weapon's normal range increment, you incur a range penalty on the attack. Because these are both untyped penalties, if you make multiple attacks at a faraway target, you'd apply both the multiple attack penalty and the range penalty to your roll.
Once you've identified all your various modifiers, bonuses, and penalties, you move on to the next step.

When creating your character and adventuring you'll record the total modifier for various important checks on your character sheet. Since many bonuses and penalties are due to the immediate circumstances, spells, and other temporary magical effects, you typically won't apply them to your notations.
For example, the number you write down for your attack modifier with your doshko would likely be your Strength modifier + your proficiency bonus with martial weapons. Your spell attack modifier is typically just your spellcasting attribute modifier + your proficiency bonus, and your spell DC is usually the same number + 10.
Item bonuses and penalties are often more persistent, so you'll often want to record them ahead of time. For instance, if you upgraded to a tactical doshko, you'll want to add the +1 item bonus into your attack modifier with the doshko since you'll include that bonus every time you attack with that weapon.