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"Differential analog voltage inputs allow increasing the common-mode rejection and offsetting the analog zero input voltage value. In addition, the voltage reference input can be adjusted to allow encoding any smaller analog voltage span
to the full 8 bits of resolution."
Sometimes you have a single ended signal and sometimes you have a differential signal. For instance, the output from a strain gauge load cell (used in weighing systems as the ones you find in supermarkets) is differential, as in all devices that use a full bridge configuration as sensor. So, the application will define if you go single or differential.